TWI342310B - Aminothiazoles and their uses - Google Patents

Description

1342310 IX. Description of the Invention: [Technical Field to Which the Invention Is Applicable] The present application describes organic compounds for treating, preventing, and/or ameliorating diseases. [Prior Art] Since the discovery of penicillin, pharmaceutical companies have produced a variety of antibacterial agents to combat various bacterial infections. In the past few years, the emergence of several types of bacterial resistance against these antibiotics has been very rapid. Multidrug resistance in these bacterial pathogens can also be attributed to mutations that lead to more toxic clinical isolates. Perhaps the most annoying thing is resistance to vancomycin, an antibiotic that is generally considered to be the last resort for serious Gram-positive infections. This is especially true for certain Gram-positive pathogens, such as staphylococci, pneumococci, and enterococci (S. Ewig, Antibiotika-Resistenz bei).

Erregern ambulant erworbener Atemwegsinfektionen _ (Antibiotic resistance in pathogens of outpatient-acquired respiratory tract infections); Chemother. J. 2002,11,12-26,F. Tenover's Development and spread of bacterial resistance to antimicrobial agents: an overview; Clin. Infect. Dis, September 15, 2001, 33 Supplement 3, 108-115) and Staphylococcus, Streptococcus, Mycobacterium, Enterococcus, Rod The same serious problems of Corynebacterium, Borrelia, spore 121012. bacillus, Chlamydia, Mycoplasma and the like are found worldwide. The more toxic anti-methoxybenzoic acid methicillin Staphylococcus aureus (MRS A) was gradually increased in the isolate. Because of the vancomycin-resistant organisms, most MRS A strains are resistant to most conventional antibiotics, but MRSA strains remain sensitive to vancomycin. However, given the increasing reports of vancomycin-resistant clinical isolates and the continuing problem of bacterial resistance, new molecular entities are urgently needed to effectively counter Gram-positive organisms that have emerged and are currently problematic. This emerging multi-drug resistance has recently rekindled interest in finding new structural antibiotics that inhibit or kill these bacteria. SUMMARY OF INVENTION The industry also needs

Tu activity method. New treatments and therapies in the industry for bacterial infections for treating or preventing or ameliorating - or multiple bacterial infections In one aspect, the invention provides a compound of formula I: 121012.doc 1342310

121012.doc 1342310

In still another aspect, the invention provides a compound of formula III:

G-J

III. In still another aspect, the invention provides a compound of formula IV:

A’

121012.doc -9- 1342310

In yet another aspect, the invention provides a compound of formula v:

In another aspect, the invention provides a compound of formula VI

R5 〇 In still another aspect, the invention provides a compound of formula VII: 121012.doc -10- 1342310

(R

In still another aspect, the present invention provides a

121012.doc -11 - VIII. In another aspect, the invention provides a method of treating a bacterial infection, wherein the treatment comprises administering to a subject in need thereof a pharmaceutically acceptable amount of Formula I, II, III, IV, V, VI, Compound VII or VIII to treat the bacterial infection. In another aspect, the invention provides a method of treating a condition associated with EF_TU, wherein the treatment comprises administering to a subject in need thereof a pharmaceutically acceptable amount of Formula I, II, ΠΙ, IV, V, Compound VI, VII or VIII' for the treatment of conditions associated with EF-Tu.

In still another aspect, the invention provides a method of treating, inhibiting or preventing EF-Tu activity in an individual in need thereof, the method comprising administering to the individual a pharmaceutically acceptable amount of Formula I, hydrazine, a compound of In, IV, V, VI, VII or VIII. In one embodiment, the bacterial infection of an individual in need thereof is treated. In another aspect, the invention provides a method of treating, inhibiting or preventing bacterial activity in an individual in need thereof, the method comprising administering to the individual a pharmaceutically acceptable amount of π, ΠΙ, IV, V A compound of formula VI, VII or VIII wherein the compound interacts with any target in the bacterial life cycle. In one embodiment, the target line EF-Tu. In another aspect, the invention provides a method of treating a bacterial infection in an individual, wherein the treatment comprises administering to a subject in need thereof a pharmaceutically acceptable amount of Formula I, II, III, IV, V, VI, A compound of VII or VIII and a pharmaceutically acceptable carrier for treating the bacterial infection. Still in another aspect, the invention provides a method of treating a bacterial infection, wherein the treatment comprises administering to a subject in need thereof a pharmaceutically effective combination with other therapeutic agents in a pharmaceutically effective 121012.doc.12·1342310 A compound of the formula i, π, ΠΙ, Iv, v VI, VII or VIII is administered to treat the bacterial infection. In one embodiment, a compound of formula I, II, ΠΙ, IV, V, VI, νπ or VIII and other pharmaceutical agents are administered as part of the same pharmaceutical composition. In another embodiment, a compound of formula I, π, Ιπ, Ιν, V, VI, VII or VIII and other therapeutic agents are administered as separate pharmaceutical compositions, and the compound is administered prior to administration of the other agent, At the same time or later. In another aspect, the invention provides a packaged bacterial infection therapeutic drug packaged by Formula I π, ΠΙ, IV, V, VI, VII, or together with instructions for the use of an effective amount of the compound to treat a bacterial infection. VIII constitutes. In another aspect, the invention provides a method of treating acne in an individual in need thereof, wherein the treatment comprises administering to the individual a pharmaceutically acceptable amount of Formula I, II, III, IV, V, Compound VI, VII or VIII. In still another aspect, the invention provides a pharmaceutical composition comprising a compound of Formulas I, II, III, IV, v, VI, Vn4VIII and at least one pharmaceutically acceptable carrier or diluent. [Embodiment] The present invention relates to a compound such as a sulfur-containing peptide compound and an intermediate thereof, and a pharmaceutical composition comprising the same for treating a bacterial infection. The invention also relates to a compound of the invention or a composition thereof as a modulator of the elongation factor EF_TU. These compounds are specifically used to interfere with the life cycle of the bacteria and to treat or prevent bacterial infections or physiological conditions associated therewith. The present invention also relates to a group for inhibiting EF-Tu activity in a cell or treating or preventing bacterial infection in a patient using the compound of the present invention or a pharmaceutical composition or kit thereof. 121012.doc 13 !34231〇

The method of treatment. In one aspect, the invention provides a compound of formula I:

And pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, constrained isomers or racemates thereof, including Its pyridine N-oxide; wherein A is selected from the group consisting of: bond, hydrazine, -(CH2)-, -C(alkyl)2-, -(CHJn, -[C(alkyl, -( Cycloalkyl)-, -(aryl)-, -(heteroaryl S)-, -C(0)-, -C(0)C(0)-, -C(0)0-, -C( 0) N(R8a)-, -S(0)2-, -S(0)-, -S(0)2N(R8a)-, -S(0)N(R8a)-, -C(=NR8 N(R8a)-, -C(=NR8)N(R8a)C(0)-, -C(=NR8)-, -C=CC(0)-, -C = CC(0)〇- ' -C=CC(0)N(R8a)-; 121012.doc -14· 1342310 G does not exist, or is selected from the group consisting of: H, [C(R)(Rb)]x-〇-[C( Ra)(Rb)]y- '-tc(Ra)(Rb)]xN(R8a)- [C(Ra)(Rb)]y-,·(cycloalkyl)_,-(heterocyclic-(aryl) Heteroaryl; J is selected from the group consisting of Η, F, 〇·alkyl, N(R8a) 2, N+(R8a)3, N(R8a)C(0) alkyl, C02H, C ( =〇)N(R8a)2, C〇2_ alkyl, P(〇)(〇H)2, p(〇)(〇-alkylh and substituted nitrogen-containing heterocycle; ^ is selected from the following composition Group: Η, alkyl, f, C〇2H , C (v 炫 base, -N (R!) 2, -OR1, -(CH2) 〇-4-J and -R4b;

Rb is selected from the group consisting of H, alkyl and F; χ and y are each independently an integer between 0 and 10; R1 is selected from -H, -C(alkyl)2-J, -R4b; R2a is selected from the group consisting of hydrazine, substituted or unsubstituted alkyl, OH, OR4a, 〇C(0)R4a, 0C(0)N(R8a)2, and N(R8a)2 · R2b The group consisting of a non-existent, anthracene and an alkyl group is selected, or RZa and may be formed together = 〇 or =NH; R3 and R12 are each independently selected from the group consisting of hydrazine, ruthenium ruthenium R4b, -GJ and N ( R8a) 2 ; 1143 is selected from the group consisting of ruthenium and alkyl; R4b is selected from the group consisting of alkyl and _(CH2-CH2-〇-)n_R9, wherein the ratio is equal to or greater than 60,000. For example, 15 (10), 1,000, 2,000, 3,000, 4,000, 5, 〇〇〇, 1 〇〇〇〇, 2 〇〇 (10) 30,000 ' 40,000 ^ 50,000 ^ 60,000; R5 is selected from the group consisting of ruthenium, alkyl and R4b R8 is selected from the group consisting of ruthenium, CN, N〇2, alkyl, ring p 121012.doc -15- 1342310 base and so2-alkyl; R does not exist, or 4b, free H, - (院Base)_, _(cycloalkyl)-, C(alkyl)2-J, -R4bM Wherein R 8a may also be cyclized with an atom to which ru is bonded to form an aromatic, non-pen 4 non-fragrance group and may comprise a 3, 4, 5, 6 or 7 membered ring of one or more heteroatoms, The ring may be further substituted one or more times with the same or different substituents; and R9 is selected from the group consisting of hydrazine, alkyl and ch2C02H.

In one embodiment of Formula I, R2b, R4b, and R5 are Η and the ruler is "CH3." In another embodiment of Formula I, R2b, R4b, and R5 are Η, R4V^, Ch3, and R12 are CH2 _〇_CH3. In another embodiment, Formula I is a compound of Formula 11:

121012.doc

N-A

II • 16-1342310 and its pharmaceutically acceptable salts are indicated > In another aspect, the invention provides a compound of the formula Ιπ:

R3, CO Η C κι

, stereoisomers, spins, restriction configuration isomers and pharmaceutically acceptable salts thereof, enantiomeric isomers, tautomers, diastereomeric or racemic forms, Including other pyridinium-tellurides; wherein R2a > R2b > r3 ' R4a ' R4b ' R5 > R > 2 , A, G and J have the meanings described for formula 1, and ring L is selected from the ring a group consisting of an alkyl group, a heterocyclic ring, a pen* cold group and a heteroaryl group, all of which are substituted by the -j in the case of the formula II, in which the R2b D 4b and the R5 system are And 11 "System 121012.doc • 17· 1342310 CH3 In another embodiment of Formula III, R2b, R4b & R5 are Η, the ruler is "ch3, and R12 is CH2-0-CH3. In another embodiment, Formula III is a compound of Formula IV:

And pharmaceutically acceptable salts thereof, wherein the rings L, A, G and J all have the meanings indicated for the formula. In another aspect, the invention provides a compound of formula V: 121012.doc • 18· 11342310 R1 ΓΛ

\ r N—A, g~j

Among them, A-G-J is Rla;

Wherein R1, 1113 and 1123 are each independently selected from the group consisting of: H' substituted or unsubstituted alkyl, alkyl aryl, heteroalkyl, heterocyclyl, heteroaryl, aryl-hetero Aryl, alkyl.heteroaryl, cycloalkyl, morphoxy, alkyl-aryloxy, aryloxy, heteroaryloxy, heterocyclooxy'cyclo- alkoxy, amine, alkylamine Alkyl, arylamino, alkyl-arylamino, arylamino, heteroarylamino, cycloalkylamino, carboxyalkylamino, aryloxy and heterocyclylamino; All of them may be further independently substituted one or more times by Z1 and z2; wherein are alkyl, alkenyl, alkynyl, cycloalkyl, cyclod-heptyl, heterocyclyl, heterocyclylalkyl, aryl Alkyl, alkylaryl, arylalkyl, arylheteroaryl, heteroaryl, heterocyclylamino, alkylheteroaryl 121012.doc •19- 1342310 or heteroarylalkyl; wherein z1 is Independently substituted by one or more Z2 moieties which may be the same or different and independently selected; wherein z2 is a hydroxyl group, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, a sulfur, an alkylthio group, an arylthio group, an amine Base

Amino, arylamine, alkylsulfonyl, arylsulfonyl, alkylsulfonylamino, arylsulfonylamino, carboxyl, alkanecarbonyl, decylamino, alkoxycarbonylamine Alkoxycarbonyloxy, alkylureido, arylureido, dentate 'cyano, ketone, ester or nitro; wherein each of the alkyl, alkoxy and aryl groups may be unsubstituted Or, as the case may be, independently substituted by one or more moieties which may be the same or different and independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, heterocyclyl, heterocycle Alkyl, aryl, alkylaryl, arylalkyl, arylheteroaryl, heteroaryl, heterocyclylamino, polyheteroaryl and heteroarylalkyl; or R1 and Rh The 3, 4, 5, 6 or 7 membered ring which is aromatic or non-aromatic and which may comprise one or more heteroatoms, wherein the ring may be substituted one or more times with the same or different substituents.

In one embodiment of Formula V, the '1^23 series. In another embodiment of the compounds of the invention, ... or singular, and A.G-J, to form hydrazine, or together form a functional group selected from the group consisting of:

121012.doc -20- 1342310

121012.doc -21 - 1342310

12l012.doc -22- 1342310

In another embodiment of the compounds of the present invention, R1 is hydrazine, and Α-G-J-A^r13 forms a functional group selected from the group consisting of 〇, 〇,

〇 , 〇 , 〇 , 〇 , 〇 , 〇

〇 and 〇 wherein R13 is selected from the group consisting of hydrogen, hydroxymethyl and amine sulfhydryl groups or is selected from the group consisting of 歹|j:

121012.doc -23- 1342310

121012.doc -24- 1342310

Integer: 1-500, l, 〇〇〇, 2,000, 3,000, 4, 〇〇〇, 5, 〇〇〇, 10,000, 20,000, 30, 〇〇〇, 4 〇, 〇〇〇, 50,000 '6〇 , hehe. In another embodiment of Formula I or III, the core pyridine functional group is an N-oxide of the formula:

In one embodiment of the compounds of the invention, when J is not F, the J series is bonded to hydrazine or N. In another embodiment, when Rb is not F, Ra is _(Rl)2. Formulas I, II, III, IV and V (including pharmaceutically acceptable salts thereof, as well as enantiomers, stereoisomers, rotamers, tautomers, diastereomers, limitations thereof) Preferred embodiments of the configuration isomers or racemates, including the N-D specific pyridine-oxides thereof, are shown in Tables A and B below, and are also considered to be "the compounds of the invention - the compounds of the invention herein also referred to For, antibiotics " and "ef_ Tu inhibitors". In still another aspect, the present invention provides a compound of the formula: 01012.doc -25- 1342310

VI and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, constrained isomers or racemates, Including its pyridine N-oxide;

R is selected from the group consisting of NCR, _ (heteroaryl group; lanthanide-bonded or selected from the group consisting of _c: -C(0)-'-c(〇)C(〇)-C〇)0 - > -C(〇)N(R8a)- ^ -S(〇), _ , -S(〇)N(R", 8 r)2, 〇)-, -s(〇)2n(r , • C(=NR8)N(R8a)C(0)-, Sichuan(r)-, -c(=nr8)n(r8, 0, -C(=Nr8)', -C=CC(0) -, p C(0)N(R8"· ; 'C==cC(0)0-, -C=c Group: _[C(Ra)(Rb)] G does not exist, is selected from the following 12I012 .doc -26· 1342310 ' -[C(Ra)(Rb)]xC(Ra)=C(Ra)-[C(Ra)(Rb)]y- > -[C(Ra)(Rb)] X- 〇-[C(Ra)(Rb)]y- and -[C(Ra)(Rb)]x_N(R8aHC(Ra)(Rb)]y·, or a group selected from the group consisting of cycloalkyl _, _ (heterocyclic) _, _ (aryl) _ and _ (heteroaryl)-, each of which has 〇 4 substituents; Q does not exist, is selected from the group consisting of: _c ( 〇)_[c(Ra)(Rb)]x· , -C(0)-[C(Ra)(Rb)]xC(Ra)=C(Ra)-[C(Ra)(Rb)]y -, _C(0)-[C(Ra)(Rb)]x-〇-[C(Ra)(Rb)]y• and _c(0)-{N(R8a)-[C(Ra)( Rb)]y}p- , or selected from the group consisting of: (cycloalkyl)·, _(heterocyclic)_, _(aryl)-, -(heteroaryl)·, -C(0 )-(cycloalkyl _, _(:(0)-(heterocyclic)-, -C(O)-(aryl)- and -C(0)-(heteroaryl)_, each of which has 〇_4 substitutions The group J is selected from the group consisting of hydrazine, Cw alkyl, halogen, Cm alkoxy, thiol, amine, mono- and bis-Cl4 alkylamino, tri-Cl.4 alkyl, alkane Base, c〇2H, C(=0)N(R8a)2, CH2C02H, CH2C(=0)N(R8a)2, cOz-Cw alkyl, C(0)Cn4 alkyl, p(o)(oh 2, p (〇) (〇_Cl 4 alkyl) 2, c. 4 alkylalkylcycloalkyl) and C. 4 extension of the base - (heterocyclic), the heterocyclic ring can be substituted 〇 _ 4 1; is selected from the group consisting of hydrazine, alkyl, F, C02H, C02-alkyl, -N(R丨)2, -〇R丨, -(CH2)〇" and simple; R Is selected from the group consisting of ruthenium, ruthenium and ρ; ρ is 0, 1, 2 or 3; each occurrence of X and y is independently selected from an integer between 丨 _ i ;; R1 each time When present, they are independently selected from _H, via; substituted alkyl and 12I012.doc • 27-1342310 R2 hydrogen, cN6 alkyl, hydroxyCl-6 alkyl, Ci6 alkoxy, alkyl C3-7 Alkyl CG.4 alkyl, aryl cG_4 alkyl or a residue of the formula: R3

The r3 r3 ruler "is selected from the group consisting of H, 6 alkyl, 〇H, 〇R4a, 〇C(〇)R4a, 〇C(0)N(R8a)2 and N(R8a)2;

R2bSH or C,·6 alkyl, or a ruler "in combination with a ruler to form an oxo or imido group; R3 and R12 are each independently selected from the group consisting of H, halogen OR4b, -GJ and N (R8a) 2 ; The ruler "selected from the group consisting of ruthenium and glaze; the ruler 415 is selected from the group consisting of alkyl and -(CH2-CH2-〇_)n_R9, wherein the following integers are: 1-500 , 1,000, 2, _, 3 〇〇〇, 4 〇〇〇,

5,000, 10,000, 20, _, 3 〇, _, 4 〇, _ ' 5 〇, _ or 60,000, or an average of the integers of the following values: (eight), 1,000, 2,000, 3, _, 4, 〇〇〇, 5 〇〇〇, 1 〇〇〇〇, 2 〇, coffee, 30,000 '40,000 - 50,000^60,000; R5 is selected from the group consisting of hydrazine, alkyl and; R8 is selected from the group consisting of: H, CN, n〇2, Cw alkyl, (: 3.7 cycloalkyl and so2-Ci.6 alkyl;

Ra is absent or selected from the group consisting of H, k alkyl, C ring cyclyl, I substituted C 丨 及 and Rn, or two cardiac groups = 121012.doc -28- 1342310 Together, a saturated, unsaturated or aromatic ring having 3 to 7 ring atoms may be formed, the ring may be substituted 〇4 times; and R9 is selected from the group consisting of hydrazine, alkyl and CH2C02H. Certain compounds of formula VI include those compounds wherein R2 is a residue of the formula:

Ruler 23 is selected from the group consisting of hydrazine, C丨-6 alkyl, OH, 〇r", 0C(0)R4a, 〇C(〇)N(R8a)2 and N(R8a)2; and R H or a Ci_6 alkyl group, or combined with R2b to form an oxo or imido group. Other compounds of formula VI include those wherein R2b, ruthenium and Rs are η, and R is "CH3". Certain other compounds of formula VI include those in which R2b, R4lR5, r, r4^ch3, and R12 are CH2-0-CH3. Other compounds of formula VI include those wherein R21〇H or OAC and R2b#H. Still other compounds of formula VI include wherein A is c(0), C(0)0 or C(0)NH, G is C4-7 cycloalkyl, Q is absent, and KfC〇2H or CC^Ci·4 The compounds of the base. Other compounds of formula VI include those wherein r#n(r1)_ag_qj, and A-G-Q-J form η or together form a functional group selected from the group consisting of: 121012.doc •29- 1342310

1342310

121012.doc •31 1342310

And Α-G-Q-J forms a functional group selected from the group consisting of

^Y〇, r13 person f eight R13 and other compounds: ο , 〇 , 〇 , ΰ ,

Wherein R13 is selected from the group consisting of hydrogen, hydroxymethyl and aminomethyl groups or a group selected from the group consisting of:

-32·121012.doc i 1342310

121012.doc -33- 1342310

Integer of η 歹丨]: 1-500 '1,000, 2,000, 3,000, 4,000, 5,000, 10,000, 20,000, 30,000 '40,000, 50,000 or 60,000, or an average of the integers of the following values: 1-500, 1.000 > 2,000 > 3,000 ' 4,000 ' 5,000 ^ 10,000 ' 20,000 ' 30.000 ' 40,000 ' 50,000^ 60,000 -

Certain preferred compounds of formula VI include, but are not limited to, compounds of formula VII: 121012.doc 34- 1342310

And pharmaceutically acceptable salts thereof. In still another aspect, the invention provides a compound of formula VIII:

A-G-Q-J

VIII 121012.doc -35- and its pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, constrained conformers Or a racemate' includes its "I-pyridyl N-oxide;

Is a 4-7 membered heteroaryl ring having 0-2 other ring heteroatoms and substituted with _a_g_q_j residues and 〇_ 4 other substituents; A is a linkage or is selected from the group consisting of -C(0)0 -, _c(0)N(R8a)-, -S(0)2-, -S(0)-, -S(0)2N(R8a)-, -S(0)N(R8a)_, _c (=NR8)N(R8a)-,·〇:(=ΝΙ18)Ν(ί183)(:(0)-, -C(=NR8)-, -〇CC(0)-, -C = CC(0 ) 0-, -C = CC(0)N(R8a).; G does not exist, is selected from the group consisting of: _[C(Ra)(Rb)]x_, -[C(Ra)(Rb)] xC(Ra)=C(Ra)-[C(Ra)(Rb)]y- . -[C(Ra)(Rb)]x-0-[C(Ra)(Rb)]y-and-[ c(Ra)(Rb)]xN(R8a)-[C(Ra)(Rb)]y-, or a group selected from the group consisting of: -(cycloalkyl)-, (heterocyclic)_, _( Aryl)- and -(heteroaryl)-' each having 0-4 substituents; Q absent, selected from the group consisting of: -C(0)-[C(Ra)(Rb) ]x-' -C(0)-[C(Ra)(Rb)]xC(Ra)=C(Ra)-[C(Ra)(Rb)]y- ' -C(O)-[C( Ra)(Rb)]x-〇-[C(Ra)(Rb)]y- and -C(0)-{N(R8a)-[C(Ra)(Rb)]y}p-, or Free group of the following: -(cycloalkyl)-, -(heterocyclic)-, (aryl)-, -(heteroaryl)-, -C(0)-(cycloalkyl)-,- C(0)-(heterocyclic)-, -C(O)- (aryl)- and -C(0)-(heteroaryl)-, each having 0-4 substituents; 121012.doc -36- 1342310 J is selected from the group consisting of H, Cm Alkyl, halogen, Ci 4 alkoxy, hydroxy, amine, mono- and di-Ci 4 alkylamino, tri-c, 4 alkyl ammonium, NCR'C^COCw alkyl, c〇2H, c ( =〇)N(R8a)2, CH2C02H, CH2C(=〇)N(R8a)2, c〇2_Ci 4 alkyl, c(〇)Ci 4 alkyl, P(0)(0H)2, P(〇 (0_Ci 4 alkyl) 2, alkyl (cycloalkyl) and C 〇 4 alkyl (heterocyclic), the heterocyclic ring may be substituted 〇 4 times; 1 ^ is selected from the following composition Group: H, alkyl, F, C02H, C〇2-alkyl, -N(Ri)2, -OR丨, _(CH2). "And ^^ ; R is selected from ruthenium, ruthenium and ρ a group of constituents; p is 0, 1, 2 or 3; each occurrence of X and y is independently selected from an integer between 〇_丨〇; each occurrence of R1 is independently selected from -H , alkyl substituted by j and _R4b. R2 is hydrogen, Cw alkyl 'hydroxy Ci 6 alkyl 'Cl 6 alkoxy Cq-6 alkyl, C 3-7 cycloalkyl CQ-4 alkyl, aryl cG 4 alkyl or a residue of the formula: R3 R3

Ra R3 ; R2\ R2b

X «^ is selected from the group consisting of Η, C丨-6 alkyl, 〇H, OR4a, 0C(0)R4a, 〇C(〇)N(R8a)2 and N(R8a)2; 11215 11 or (: 1.6 alkyl, or R2a combined with an oxo or imido group; R3 and R12 are each independently selected from the group consisting of hydrazine, dentate, 121012.doc -37· 1342310 〇 R4b, -gj and N(R8a)2; the ruler "selected from the group consisting of H and alkyl; R4b is selected from the group consisting of alkyl and ((: Η2-0: Η2-〇-) ηι9, wherein n is the following integer: 1-500, i'000, 2 〇〇〇, 3 〇〇〇, 4 〇〇〇, 5' 〇〇〇, 10,000, 20,000, 30,000, 4 〇, _, 5 〇, _ Or 60,000, or an average of the integers of the following values: (eight), 1,000 ' 2,000 > 3,000 ' 4,000 ' 5, 〇〇〇, 1 〇, 〇〇〇, 20, 〇〇〇 30,000, 40, 〇〇〇 , 5〇, 〇〇〇 or 60,000; R5 is selected from the group consisting of ruthenium, alkyl and R4b; R8 is selected from the group consisting of Η, CN, N〇2, Ci-6 炫, C3-7 Cycloalkyl and scvcw alkyl; R8a is absent or selected from the group consisting of hydrazine, Cu alkyl a c 3-7 cycloalkyl group, a j-substituted C1-6 alkyl group, or a two-foot "residue grouped together to form a saturated, unsaturated or aromatic ring having 3 to 7 ring atoms" The compound may be substituted for 〇4 times; and R9 is selected from the group consisting of hydrazine, alkyl and ch2co2h. Certain compounds of formula VI include those compounds wherein R2 is a residue of the formula:

&23 is selected from the group consisting of hydrazine, Cl-6 alkyl, OH, OR4a, 〇C(0)R4a, 〇c(〇)N(R8a)2 and N(R8a)2; and 121012. Doc-38- 1342310 R2b is H or C1-6 alkyl, or Rule 23 and 1121) are combined to form an oxo or imido group. Still other compounds of formula VIII include those compounds wherein R2b, R4b&R5 are indole, and R41CH3. Certain other compounds of formula VIII include R2b, R4lR5, R, R4UH3, and R丨2, Ch2_〇_CH3

And other compounds. Other compounds of formula VIII include those wherein R2a or 〇Ac and R2b are oxime. Other compounds of the formula νιπ include octa C(O), C(0)0 or C(0)NH, G-system C4-7 cycloalkyl, presence and j-system C〇2H or CC^Cw These compounds.

(DJ Formula viii is still other compounds including / where the residue is via A_G_Q_

The (four) base ring substituted by J; mQ] together form a ruthenium or a compound which forms a functional group selected from the group consisting of:

121012.doc •39· 1342310

121012.doc • 40- 1342310

Other compounds of formula VIII include imidazolyl rings wherein the / residue is substituted with AGQJ; and AGQJ-formed from 121012.doc -41 - 1342310 /丫, 彳3 ^γ〇^13 ^γΝ^13 The compounds of the group's functional groups: 〇, 〇, 〇

And 〇

Wherein R13 is selected from the group consisting of hydrogen, hydroxyindenyl and aminomethyl or selected from the group consisting of:

121012.doc -42- 1342310

121012.doc -43- 1342310 Integer of η 歹 歹 ij: 1-500 '1,000, 2,000, 3,000, 4,000, 5,000, 10,000, 20,000, 30,000 '40,000, 50,000 or 60,000 or an integer of the following values Average: 1-500, 1,000, 2.000 ' 3,000 ' 4,000 > 5,000 > 10,000 ' 20,000 ' 30,000 > 40.000 ' 50,000 or 60,000 °

121012.doc -44- 1342310

121012.doc -45- 1342310

121012.doc -46- 1342310

121012.doc ·47· 1342310

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Table B

η = 1 - 60,000 In certain embodiments, another feature of the compounds of the invention is as a modulator of EF-Tu, including prokaryotic EF-Tu, and especially bacteria EF-Tu. In a preferred embodiment, the compounds of the invention are EF-Tu inhibitors. The term "bacterial infection" as used herein includes, but is not limited to, bacterial infections occurring in mammals 121012.doc -59-1342310, fish and birds, and diseases associated with bacterial infections, which can be administered by Antibiotics (e.g., compounds of the invention) are treated or prevented. In addition to treating infections caused by Staphyloccocus aureus, Strept〇c〇ccus pneuin〇niae, Mycobacterium tuberculosis, and Enterococci resistant multi-drug strains, the compounds of the invention are also For the treatment of infections caused by other bacteria including, but not limited to, Clostridium difficile, Propionibacterium acnes, Bacteroides fagiles, Neisser's gonorrhea Neisseria gonorrhoeae, Branhamella catarrhalis, Haemophilus influenzae, E. coli, Pseud〇m〇nas aeruginosa, common bacillus (pr〇teus vulgaris), Klebsiella pneumonia and Chlamydia trachomatis 〇

Such bacterial infections and conditions associated with such infections include (but are not limited to) the following: hemorrhoids; rosacea; skin infections; pneumonia; otitis media; sinusitis; bronchitis; tonsillitis and with blood stasis by Streptococcus pneumoniae Bacterial, Moraxella catarrhalis, Staphylococcus aureus, Peptostreptococcus spp., or Pseudomonas spp. infection of mastoiditis; pharyngitis; rheumatic fever and Streptococcus pyogenes, C and G group streptococci, Clostridium diptheriae or Actinobacillus haemolyticum infection associated with glomerulonephritis; and -60-12I012.doc by Mycoplasma pneumoniae (Mycoplasma Pneumoniae), Legionella pneumophila, Streptococcus pneumoniae, Haemophilus influenzae or Chlamydia pneumoniae infection-related respiratory infections; uncomplicated skin and soft tissue infections; abscesses and osteomyelitis and Staphylococcus aureus, coagulase-positive staphylococci (coagulase_p〇s〗 〖tive staphyloco Cci) (ie, s. epidermidis, S_ hemolyticus, etc.), S. py0genes, S. agalactiae, streptococcal group CF (Micro-Streptococcus streptococci), Viridans streptococci, Corynebacterium spp., Clostridium spp. or Bartonella henselae infection Postpartum fever, non-complex acute urinary tract infections associated with infection with S. saprophyticus or Enterococcus spp.; urethritis and cervicitis; and Chlamydia trachomatis, Haemophilus ducreyi ), Treponema pallidum, Ureaplasma urealyticum or Nesseria gonorrheae infection-related sexually transmitted diseases; and S. aureus (food poisoning and toxicity) Shock syndrome) or toxic diseases associated with group A, S, and C streptococcal infections; ulcers associated with infection with Helicobacter pylori Systemic fever syndrome associated with infection by Borrelia recurrentis; Lyme disease associated with infection with Borrelia burgdorferi; and Chlamydia trachomatis (C. trachomatis) N. gonorrhoeae, Staphylococcus aureus, Streptococcus pneumoniae (s 121012.doc *61 · 1342310 pneumoniae), Streptococcus pneumoniae, Haemophilus influenzae (H. influenzae) or Listeria spp. infection Related conjunctivitis, keratitis, and lacrimal sac k' with disseminated Mycobacterium avium complex associated with infection with Mycobacterium avium or Mycobacterium intracellulare (MAC) disease; gastroenteritis associated with infection with Campyl〇bacter jejuni; intestinal protozoa associated with infection with crypt〇Sp〇r丨dium spp·; A odontogenic infection associated with Streptococcus viridans infection; a persistent cough associated with infection with B〇rdetella pertussis; Clostridium perfringens or Bacteroides spp, infection associated with gas gangrene; skin infections caused by Staphylococcus aureus, acne bacteria; arteries associated with infection with Helicobacter pylori or Chlamydia pneumoniae Atherosclerosis or the like. Other bacterial infections and conditions that may be treated or prevented in animals associated with such infections include, but are not limited to, the following: with P. haemolytica, Pasteurella septicum (p. Multocida), Mycoplasma bovis or Bordete Ua spp. infection related to bovine respiratory diseases; and by E. coli or protozoa (world's 'coccidia') Wormtosporidia, etc.) Infection-related bovine intestinal diseases, and by Staphylococcus aureus, S. iiberis, Streptococcus agalactiae, Streptococcus mutans (s dySgalactiae), Klebsiella (Klebsiella Spp.), Corynebacterium (C0rynebacteriuin) or Enterococcus infection associated with cow mastitis; with the porcine pleuropneumonia line rod 121012.doc • 62· 1342310

Swine respiratory disease associated with infection with A. pleuropneumoniae, P. pastoris or Mycoplasma spp.; and by Escherichia coli, Lawsonia intracellularis, Salmonella Spp.) or Intestinal disease associated with infection with Serpulina hyodyisinteriae; hoof rot associated with infection with Fusobacterium spp.; and bovine metritis associated with infection with E. coli; Bovine hairy hairs infected with Fusobacterium necrophorum or Bacteroides nodosus; red eye disease associated with infection with Moraxella bovis; premature birth of cattle associated with infection with protozoa ( Aneosporium); urinary tract infections in dogs and cats associated with E. coli infection; and by Staphylococcus epidermidis, S. intermedius, coagulase neg (Staphylococcus) or septic Pasteur Skin and soft tissue infections in dogs and cats associated with bacilli infection; and dogs and goats associated with the following infections Or oral infection: Alcaligenes spp., Bacteroides spp., Clostridium spp., Enterobacter spp., Eubacterium spp., digestive bonds Peptostreptococcus spp., Porphfyromonas spp., Campylobacter spp., Actinomyces spp., Erysipelothrix spp., Rhodococcus spp., Trypanosoma spp ·), Plasmodium spp., Babesia spp., Toxoplasma spp., Pneumocystis spp., Leishmania spp. Trichomonas spp, or Prevo 121012.doc -63-1342310 (Prevotel丨a Spp.). Other bacterial infections and conditions associated with such infections that can be treated or prevented according to the methods of the present invention are described in "The Sanford Guide To Antimicrobial Therapy" 26th edition, (Antimicrobial Therapy, 1996) by Jp Sanf〇rd et al. and. Other bacterial infections and symptoms that may be treated or prevented in animals in connection with such infections include, but are not limited to, central nervous system infections, external ear infections, middle ear infections (eg, acute otitis media), dural sinus infections, eye infections. Oral infections (eg teeth, gums and mucosal infections), upper respiratory tract infections, lower respiratory tract infections, genitourinary infections, gastrointestinal infections, gynecological infections, septicemia, bone and joint infections, skin and skin structure infections, bacterial heart Anti-bacterial prophylaxis for endometritis, burns, anti-bacterial prophylaxis of surgery, immunosuppressed patients (eg patients receiving cancer chemotherapy or organ transplants) and chronic diseases caused by infectious organisms, such as arteriosclerosis. EF-Tu chaperones are required for bacterial protein synthesis. EF_Tu is one of the most abundant proteins in bacteria and is one of the most highly conserved, and in most species 'this gene replicates with the same function. When bonded to GTp, EF-Tu can form a complex with most of the amino-thiolated tRNA, which is loaded onto the ribosome. In one embodiment, the bacterial infection is associated with ef_Tu activity. Without being bound by theory, it is believed that disruption of EF-Tu protein activity by a compound of the invention will interfere with protein synthesis and thereby interfere with bacterial function and/or proliferation. Since £1?_丁11 is both in the Gram-positive and Gram-negative bacteria, the compounds of the present invention are used to treat infections of both types of bacteria. The term "conditions relating to EF-Tu," and EF_Tu related 121012.doc • 64. The condition 'includes a condition and condition associated with EF-Tu activity (e.g., disease/brother). A non-limiting example of a condition associated with EF-Tu is individual bacterial infection. ~ The present invention encompasses the treatment of bacterial infections as described above and disorders associated with eF_Tu, but the invention is not intended to be limited by the manner in which the compound is intended to perform its intended effect in treating a disease. The invention includes the treatment of a disease described herein, such as a bacterial infection, in any manner that permits treatment to occur. In certain embodiments, the invention provides a pharmaceutical composition of any of the compounds of the invention. In a related embodiment, the invention provides a pharmaceutical composition comprising any one of the compounds of the invention and any pharmaceutically acceptable carrier or excipient of any of the compounds. In certain embodiments, the invention includes a compound that is a new chemical entity. In one embodiment, the invention includes a packaged bacterial infection therapeutic drug. The packaged therapeutic drug comprises a compound of the invention packaged together with instructions for the use of an effective amount of a compound of the invention for the intended use. The compounds of the present invention are useful as active agents for pharmaceutical compositions which are particularly effective in the treatment of bacterial infections. In various embodiments, the pharmaceutical composition contains a pharmaceutically effective amount of the active agent of the present invention together with other pharmaceutically acceptable agents, carriers, fillers, diluents, and the like, and the phrase used herein, • therapeutically effective amount " The amount required to administer to a host or to a cell, tissue or organ of a host to achieve a therapeutic result, particularly an anti-bacterial infection effect (e.g., inhibit bacterial proliferation or inhibit any other bacterial infection). In other embodiments, the invention provides methods for inhibiting the activity of £17-111 protein. The method comprises contacting the cell with any of the compounds of the invention 121012.doc -65-1342310 In a related embodiment, the method further provides a compound in an amount effective to selectively inhibit the activity of the EF-Tu protein. In other embodiments, the invention provides an agent of any of the compounds of the invention for use in the manufacture of a medicament for treating a bacterial infection in an individual. In other embodiments, the invention provides a method of making a medicament comprising formulating any of the compounds of the invention for use in treating an individual. Defining the term "treatment (_),,, "treated ",, treatment (_心)" or "treatment" includes reducing or alleviating at least one condition and condition to be treated Or a symptom associated with or caused by the disease. In certain embodiments: the treatment comprises inducing a bacterial infection, followed by activation of a compound of the invention, thereby reducing or alleviating at least one symptom associated with or caused by the bacterial infection to be treated. For example, 'the treatment can be to reduce the symptoms of the disease or several symptoms or to completely eradicate the condition.

Or organisms with bacterial infections, examples of which include mammals, such as sheep, Yamagata, depiction, mice, and rabbits. In certain embodiments, the human is at risk or may be susceptible to bacterial susceptibility. In another embodiment, the term "individual" is intended to include, for example, prokaryotes and eukaryotes. Non-human systems such as humans, dogs, cattle, horses, pigs, pigs, rats, and transgenic genes, such as systemic cells that have developed, infected, and diseased diseases or conditions described herein. The compound of the seven (four) A, "," " EF-h modulator" or "EF_Tu inhibitor refers to a compound that modulates (e.g., inhibits or otherwise alters the activity of the foot). Examples of compounds that modulate EF-Tu include Formula (4), 12I0l2.doc • 66 - 1342310 Compounds of IV and V and Tables A and 8 (including pharmaceutically acceptable salts thereof and their enantiomers, stereoisomers, rotamers, mutual Isomers, diastereomers, constrained conformers or racemates. Further, the method of the invention comprises administering to a subject an effective amount of a compound of the invention for modulating EF-Tu, for example, 】, ivav, and compounds of Tables VIII and b that regulate EF-Tu (including pharmaceutically acceptable oxime and its enantiomers, stereoisomers, rotamers, tautomers, non- Enantiomers, constrained conformers or racemates. The "alkyl" includes saturated aliphatic groups, including linear alkyl groups (eg, thiol, ethyl, Propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl, decyl, etc., branched chains a group (isopropyl, tert-butyl, isobutyl, etc.), a cycloalkyl (alicyclic) group (cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl), An alkyl-substituted cycloalkyl group and a cycloalkyl-substituted alkyl group. The term "alkyl" also includes alkenyl groups and alkynyl groups. In addition, "Cx-Cy-alkyl" (where \ is 1_5 and 丫 is 2_1〇) means a specific alkyl group (straight or branched) having a specific carbon number range. For example, the 'Ci-C4·alkyl notation includes (but not Limited to) methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, isobutyl and second butyl. In addition, the term C3_6-cycloalkyl includes, but is not limited to, cyclopropyl a group, a cyclopentyl group and a cyclohexyl group. As discussed below, the alkyl group and the cycloalkyl group may be further substituted. "C(rcnalkyl" means a single covalent bond (cq) Or an alkyl group having 1 to n carbon atoms; for example, "Cq_c4 alkyl" means a single covalent bond or a Ci-C4 alkyl group; "CQ-C8 alkyl" Single covalent bond or base In some cases, the substituent of the alkyl group 121012.doc • 67· 1342310 is specified. For example, "Cl_C4 hydroxyalkyl" refers to a CrCU alkyl group having at least one hydroxy substituent. "alkylene" means a divalent alkyl group as defined above. Cq_C4 alkyl is a single covalent bond or an alkyl group having from 1 to 4 carbon atoms; and c〇_c6 The alkyl group is monovalently bonded or has an alkyl group having up to 6 carbon atoms. "Extend alkenyl" and "exetylene group" respectively mean a divalent alkenyl group and alkyne as defined above Base group. "Cycloalkyl" is a group comprising - or a plurality of ring members in which all of the ring members are saturated and/or partially saturated with carbon, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl 'cycloheptane a base, a cyclooctyl group, a ruthenium group, a decyl-caiyl group, an octahydro-indenyl group, and a partial saturated variation of the foregoing, such as cyclohexenyl. The ring base does not include an aromatic ring or a heterocyclic ring. Some cycloalkyl groups are Cs-C8 cycloalkyl groups wherein the group contains a single ring having from 3 to 8 ring members. (Cs-C8 decyl Wo-C: 4 alkyl) is a C3.C8 cycloalkyl group attached via a single covalent bond or a Ci-C4 alkyl group. In some aspects, Cw The ruthenium group is substituted one or more times (or preferably between i and 5 times) independently of a substituent selected from the group consisting of a dentate atom, an aryl group, a heteroaryl group, a tridentate methyl group, C _ 4-alkoxy or Cl 4 -alkyl. In addition, the hospital base (such as methyl, ethyl, propyl, butyl, pentyl, hexyl, etc.) includes "unsubstituted alkyl, and &quot The substituted alkyl group, the latter of which is the alkyl group having one of the f-hydrocarbon backbone or the substituent from the nitrogen on the carbon'. This allows the molecule to perform its intended function. Substituting " is intended to imply a moiety having a substituent on a hydrogen of one or more atoms (e.g., C, 〇 or N) of a substituted molecule. Such substituents may include (e.g., 121012.doc -68· 1342310) oxo , an alkyl group, an alkoxy group, a dilute group, an alkynyl group, a hydroxyl group, a hydroxyl group, a hydrylcarbonyloxy group, an arylcarbonyloxy group, an alkoxycarbonyloxy group, an aryloxycarbonyloxy group, a carboxylate group, an alkane Alkylcarbonyl Arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, amine Including alkylamino, dialkylamino, arylamino, diarylamine and alkylarylamine), mercaptoamine (including alkylcarbonylamino, arylcarbonylamino, amine) Alkyl and ureido), fluorenyl, imido, fluorenyl, thiol, arylthio, thiohistadyl, sulphate, sulphate, sulphate, sulfonamide, Sulfonamide, nitro, trifluoromethyl, cyano, azido, heterocyclyl, aryl, guanyl, phenyl, phenyl, hexazaazine, cyclopentyl Burning, cyclohexanol>, ° ratio bite, 5H-tetrasodium, triple spit, hexahydrou ratio bite or aromatic or heteroaromatic moiety, and any combination thereof. Other substituents of the invention not intended to be limited Examples include a moiety selected from the group consisting of a straight or branched alkyl group (preferably C^-Cs), a cycloalkyl group (preferably c3-C8), an alkoxy group (preferably CVC6), a thioalkyl group (compared Good Cl_c6), Base (preferably (VC6), alkynyl (preferably CVC6), heterocyclic, carbocyclic, aryl (eg phenyl), aryloxy (eg phenoxy), aralkyl (eg benzyl), aromatic An oxyalkyl group (e.g., a oxyalkyl group), an aryl acetamino group, a arylaryl group, a heteroarylalkyl group, a pyrenyl group, and an aryl group or other such a aryl group, a heteroaryl group a benzyl or heteroaryl group, (CR, R") 0_3NR, R" (e.g., -NH2), (cr, r") 〇_3cn (e.g., -CN), -N〇2, dentate (for example, _F, _C1, - or ..., (CR'R") 0_3c (halogen) 3 (eg _CF3), (CR, R") 〇.3CH (self-prime) 2, (CR'R") 0.3CH2 ( i)), (CR'R'Jo.sCONR'R", (CR'R") 0.3 121012.doc 1342310 (CNH)NR'R", (CITino.WO^NR.R", (CR.R" ). 3CH〇, (cr, r, v3o(crir")0-3h, (cr'r")0.3S(o)0-3R, (for example, _s〇3H, •0S03H), (ΟΙ'ΙΠίΜΟβΙΙ'ΙΙ” )··# (eg ' _CH2OCH3 and -〇CH3) , (CR'R")〇.3S(CR'R"V3H (eg ' _SH and _SCH3), (CR'R")03〇h (eg ' -OH), (CW^COR', (Cr, R") {)-3 (substituted or unsubstituted stupid base), (CR'R'') G-3 (C3-C8 cycloalkyl) , (cr'r,,) 3c〇2r, (eg, -C〇2H) or (CR R ')〇-3〇R' group or a side chain of any naturally occurring amino acid; wherein R' and R" are each independently argon, Cl_C5 alkyl, (^, alkenyl, CyC5 alkynyl or aryl groups. These substituents may include, for example, halogen, hydroxy, alkylcarbonyloxy, arylcarbonyloxy , alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, amino group, thiol group Ik group, alkoxy group, acid group, phosphonate group , squaric acid, cyano, amine (including alkylamino, dialkylamino, arylamine, diarylamine, and alkyl) Amino), mercaptoamine (including alkylamino, arylcarbonyl, amine, mercapto and ureido), sulfhydryl, imine, anthracene, fluorenyl, alkylthio, aromatic sulfur Base, thiodecanoate, sulfate, sulfonate, sulfonamide, extender amine, exact, trimethyl, cyano, azide, heterocyclic or aromatic or heteroaromatic Part and any combination thereof. In certain embodiments, the carbonyl moiety (c=0) may be further derivatized with a hydrazine moiety, for example, the 'aldehyde moiety may be derivatized to its 肟GC=N_〇H) analog. The skilled artisan will appreciate that (if appropriate) the substituted moiety on the hydrocarbon chain may itself be substituted. The cycloalkyl group may be further substituted, for example, with the above substituents. "Aralkyl" is partially substituted with an aryl group ( For example, benzyl (ie, benzyl)). The term "alkenyl" includes lengths and possible substituents similar to those of the above alkyl group: 121012.doc -70-1342310 saturated aliphatic group, but which contains at least one Double bond. For example, the term "dilute group" includes a linear alkenyl group (eg, vinyl, Alkenyl, butenyl, pentenyl, hexenyl, heptenyl octenyl, nonenyl, decenyl, etc.), branched alkenyl group, cycloalkenyl (alicyclic) group ( a cyclopropenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenylcyclooctenyl group, a cycloalkenyl group substituted with an alkyl group or an alkenyl group, and an alkenyl group substituted with a cycloalkyl group or a cycloalkenyl group The term alkenyl further includes an alkenyl group containing one or more carbons of an oxygen, nitrogen, sulfur or phosphorus atom in place of the hydrocarbon backbone. In certain embodiments, a straight or branched alkenyl group has 6 or fewer carbon atoms in its backbone (e.g., C2_C6 for a straight chain and CrC6 for a branched chain). Also, the cycloalkenyl group may have 3 8 carbon atoms in its ring structure, and more preferably 5 or 6 carbons in the ring structure. The term c2-C6 includes an alkenyl group containing 2 to 6 carbon atoms. Further 'the term alkenyl includes "unsubstituted dilute base" and "substituted dilute base""thelatter" the latter refers to an alkene having a substituent of one or more hydrogens on the carbon replacing the hydrocarbon backbone. Base part. Such substituents may include, for example, an alkyl group, a blocked group, a dentate, a hydroxyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an alkoxycarbonyloxy group, an aryloxycarbonyloxy group, Carboxyl, alkylcarbonyl, aryl)k., alkoxy, alketyl, anthranyl, alkoxy, alkylthio, alkoxy, phosphoric acid Root, phosphonate, phosphinate, fluoro, amine (including alkylamino, dialkylamino, arylamino, diarylamine and alkylarylamine), fluorenyl Amino group (including alkylcarbonylamino group, arylcarbonylamino group, amine carbaryl group and ureido group), fluorenyl group, imido group, fluorenyl group, alkylthio group, arylthio group, thiocarboxylate group, sulfur 121012 .doc 1342310 Acid radical, alkylsulfinyl, sulfonate, sulfonyl, sulfonylamino, nitro, difluoromethyl, cyano, azide, heterocyclic, alkylaryl Or an aromatic or heteroaromatic moiety. The term "alkynyl" includes unsaturated aliphatic groups of varying length and possible substituents similar to those described above, but which contain at least one triple bond. For example, the term "alkynyl, includes straight-chain alkynyl groups (eg, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, decyne) a base group, a fluorene group, etc., a branched bond group group, and an alkynyl group substituted with a cyclodyl group or a _ ring group. The term alkynyl further includes alkynyl groups containing one or more carbons of an oxygen, nitrogen, sulfur or phosphorus atom in place of the hydrocarbon backbone. In certain embodiments the 'linear or branched alkynyl group has 6 or fewer carbon atoms in its backbone (e.g., 'C2_C6 for a straight chain, C3-C6 for a branched chain). The term C2-C6 includes alkynyl groups containing from 2 to 6 carbon atoms. In addition, the term alkynyl includes "unsubstituted alkynyl" and "substituted block""thelatter" the latter refers to an alkynyl group having a substituent replacing one or more hydrogens on the carbon of the hydrocarbon backbone. These substituents may include, for example, an alkyl group, an alkynyl group, a halogen, a hydroxyl group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an alkoxyoxy group, an aryloxyoxy group. Base, tickrate group, alkyl group, aryl group, alkyloxy group, amino group, alkylamino group, dialkylamino group, sulfur group, burning oxygen Base, acid-base, phosphonate, quaternary, gas-based, amine-based (including alkylamino, dimeric amine, arylamine, diarylamine, and alkylarylamine ) mercaptoamine (including alkylcarbonylamino, arylcarbonylamino, aminecarboxamyl and ureido), sulfhydryl, imine, thiol, thiol, arylthio, thiocarboxylate Acid group, sulfur 121012.doc -72-1342310 acid group, alkyl sulfinyl group, sulfonate group, sulfonyl group, sulfonylamino group, nitro group, trifluoromethyl group, aryl group, gas group, Heterocyclyl, alkylaryl, or ^-fragrance or heteroaromatic moiety. The term ", amine" or "amino" is understood to apply to a broad range of molecules, or partial or uterine groups. , as commonly understood in the industry, and can be primary, secondary or tertiary. The term "amine" or "amino group" includes compounds in which a nitrogen atom is covalently bonded to at least one carbon, hydrogen or hetero atom. The term includes, for example, but is not limited to, "alkylamino", "arylamino,,,,, diarylamino", "alkylarylamine", "Alkylaminoaryl","arylaminoalkyl", "alkylaminoalkyl decylamine", "decylamine" and "aminocarbonyl". The term "hospital amine" includes groups and compounds in which a nitrogen bond is bonded to at least one other alkyl group. The term "dialkylamino," includes groups wherein the nitrogen atom is bonded to at least two other alkyl groups. The term "arylamino" ""diarylamine group 11 includes groups wherein the nitrogen is bonded to at least one or two aryl groups, respectively. The term "alkylarylamino""Alkylaminoaryl" or "arylaminoalkyl" refers to an amine group bonded to at least one alkyl group and at least one aryl group. The term "alkylaminoalkyl" refers to an alkyl, alkenyl or alkynyl group bonded to a nitrogen atom and which is also bonded to the alkyl group. "Or "Aminocarbonyl" includes a compound or moiety comprising a nitrogen atom bonded to a carbon of a carbonyl or thiocarbonyl group. The term includes "alkylaminocarbonyl" or "alkane Alkylcarbonyl" group, which includes an alkyl, alkenyl, aryl or alkynyl group bonded to an amine group and bonded to a carbonyl group, which includes an aryl group Aminocarbonyl and aryl 121012.doc • 73- 1342310 carbonylamino group, these include a carbon bonded to an amine group and bonded to a carbonyl or thiocarbonyl group Or a heteroaryl moiety. The term "alkylaminocarbonyl", "alkenylaminocarbonyl", "alkynylaminocarbonyl", "arylaminocarbonyl", "alkylcarbonylamino" ;, "Alkenylcarbonylamino" "alkynyl-based alkaloid" and "aryl arylamino" are included in the term "bristamine" Indoleamine also includes ureido (aminocarbonylamino) and amino phthalate (oxycarbonylamino). The term "aryl" includes both 5 and 6 membered mono-cyclic aromatic groups. For each of the ® groups, the 5 and 6 membered mono-cyclic aromatic groups may include up to 4 heteroatoms, for example, phenyl, valprone, gnach, sigh, sigh, isosal, imidazole , triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like. Further, the term, aryl " includes polycyclic aryl groups, for example, tricyclic , bicyclic, for example, naphthalene, benzoxazole, benzodiazepine, benzothiazole, benzimidazole, benzothiophene, methylene dioxyphenyl, sulfonate, isoindene, sulfhydryl, Filipino, napthridine, ° 丨 "«, benzene I and furan, hydrazine, benzofuran, deazapurine or pyridazine. The aryl group with a hetero atom in the ring structure can also be called " An arylheterocyclic ", "heterocyclic", 1 heteroaryl" or "heteroaromatic". The aromatic ring may be at one or more ring positions as described above Such substituents are substituted, for example, alkyl, halogen, hydroxy, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxy Acid group, alkylcarbonyl group, alkylaminocarbonyl group, aralkylaminocarbonyl group, alkenylaminocarbonyl group, alkylcarbonyl group, arylcarbonyl group, aralkylcarbonyl group, alkenylcarbonyl group, alkoxycarbonyl group, amine group Carbonyl, alkylthiocarbonyl, phosphate, phosphonate, phosphinate, cyano, 121012.doc • 74· 1342310 Amine (including amphoteric amine, dihydrolamine, arylamine, two Aromatic amine group, and aryl arylamino group), arylamino group (including alkylamino group, arylcarbonylamino group, amine carbaryl group and ureido group), fluorenyl group, imine group, Base, alkylthio, arylthio, thiocarboxylate, sulfate, alkylsulfinyl, sulfonate, sulfonamide, sulfonylamino, nitro, trimethyl, cyano An azide group, a heterocyclic group, an alkylaryl group, or an aromatic or heteroaromatic moiety. The aryl group may also be fused or bridged with a non-aromatic cycloaliphatic or heterocyclic ring to form a polycyclic ring (e.g., tetralin). The term heteroaryl, as used herein, denotes a stable monocyclic or bicyclic ring of up to 7 atoms in each ring, wherein at least one ring is aromatic and contains from about 4 heteroatoms selected from the group consisting of ruthenium, N and S. Heteroaryl groups within the scope of this definition include, but are not limited to, acridinyl, oxazolyl, porphyrinyl, quinolinolylpyrazolyl, fluorenyl, benzotriazolyl, furyl, Thienyl, benzothienyl, benzofuranyl, quinolyl, isoquinolyl, oxazolyl, isoxazolyl, fluorenyl, oxazinyl, pyridazinyl, acridinyl, pyrimidinyl, Rumyl, tetrahydroquinoline. As with the definition of the following heterocyclic ring, "heteroaryl" is also understood to include any N-oxide derivative of a nitrogen-containing heteroaryl group. It should be understood that in the case where the heteroaryl substituent is a bicyclic ring and one ring system is non-aromatic or does not contain a hetero atom, it is bonded via an aromatic ring or via a ring containing a hetero atom, respectively. The term "heterocyclic" or "heterocyclyl" as used herein is intended to mean a 5 to 1 member aromatic or non-aromatic heterocyclic ring which contains from 1 to 4 groups selected from the group consisting of 0, NAS: And includes a bicyclic group. Thus, "heterocyclyl" includes the heteroaryl groups described above as well as the dihydro and tetrahydro analogs thereof. "Heterocyclyl, other examples include 121012.doc • 75· 1342310 (but not limited to) of the following: benzimidazolyl, benzofuranyl, benzotrienyl, benzoindole, benzotriene Salivyl, benzoxenyl, benzoxanthyl, carbazolyl,. A porphyrin group, a 4-phenyl group, a furyl group, an imidazolyl group, a diazo group, a quinone group.引D基基,°引点拉拉11 Indolazinyl, 丨 丨 、, isobenzofuranyl, isodecyl, isoquinolyl, isothiazolyl, isoindolyl, naphthylpyridyl , oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxabutyryl, pyranyl, pyridazinyl, pyrazolyl, pyridazinyl, pyrido-α ratio, azine A pyridyl group, a pyridyl group, a pyrrolyl group, a pyrrolyl group, a quinolyl group, a quinolinol group, a tetrahydropyranyl group, a tetrazolyl group, and a tetrasazone. Than base, °-α-seat, sulfhydryl, °-septyl, s-trisyl' azetidinyl, 1,4-dioxalate, hexahydroazetyl, hexahydro-β ratio Azinyl, hexahydron-leptyl, pyridin-2-one, pyrrolidinyl, morphinyl, thiomorphinyl, dihydrobenzox. Sodium, monohydrobenzopyrazine, dihydrobenzobenzoyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, indanyl, dihydroisoindole , dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridyl, dihydropyrimidinyl, dihydropyrrolyl, dihydrogen Quinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazepine, methylenedioxy Base, tetrahydrofuranyl and tetrahydroanthracenyl and their ruthenium oxides. The heterocyclyl substituent can be attached via a carbon atom or via a heteroatom. The term "indenyl," includes compounds and moieties comprising a thiol group (chco) or a carbonyl group. The term "substituted thiol" includes a fluorenyl group in which one or more hydrogen atoms are replaced by, for example, the following groups: alkyl group, acetylene group hydroxy group, alkyl carbonyl group, Arylcarbonyloxy, alkoxy 121012.doc •76- 1342310 alkoxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl 'arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkyl Aminocarbonyl, dialkylamino, thiolcarbonyl, alkoxy, phosphate, phosphonate 'phosphinic acid, cyano, amine (including alkylamino, dialkylamino , an arylamino group, a diarylamine group and an alkylarylamino group), a mercaptoamine group (including an alkylcarbonylamino group, an arylcarbonylamino group, an amine formazan group and a urea group), a fluorenyl group, Imino, mercapto, alkylthio, arylthio, thiocarboxylate, sulfate, alkylsulfinyl, sulfonate, sulfonamide, sulfonamide, nitro, trifluoromethyl A cyano group, a cyano group, an azido group, a heterocyclic group, an alkylaryl group, or an aromatic or heteroaromatic moiety. The term "mercaptoamine group" includes a moiety in which a thiol moiety is bonded to an amine group. For example, 'the term includes alkylcarbonylamino, arylcarbonylamino, aminemethanyl, and ureido. The term "alkoxy" includes substituted and unsubstituted alkyl, dilute and block groups covalently bonded to an oxygen atom. Examples of alkoxy groups include decyloxy and ethoxy groups. a group, an isopropoxy group, a propoxy group, a butoxy group, and a pentyloxy group and may include a cyclic group such as a cyclopentyloxy group. Examples of the substituted methoxy group include a chiral alkane Oxyl group. These alkoxy groups may be substituted, for example, by the following groups: a dilute group, a fast group, a south group, a thiol group, an alkyloxy group, an arylcarbonyloxy group, an alkoxycarbonyl group. Oxyl, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkane Oxygen, phosphate, phosphonate, phosphinate, cyano, amine (including alkylamino, dialkylamino, arylamine, diaryl) Amino group and alkyl aryl amine I21012.doc • 77· 1342310 base), mercaptoamine group (including alkylcarbonylamino group, arylcarbonylamino group, amine fluorenyl group and gland group)' fluorenyl group Amine, mercapto, alkylthio, arylthio, thiocarboxylate, sulfate, alkylsulfinyl, sulfonate, amidoxime, sulfonamide, nitro, trifluoromethyl a cyano group, an azido group, a heterocyclic group, an alkylaryl group, or an aromatic or heteroaromatic moiety. Examples of alkoxy groups substituted by themselves include, but are not limited to, methoxy groups, Fluoromethoxy, difluoromethoxy, methoxy, dimethoxy, trisethoxy, etc. The term "carbonyl" or "carboxy" includes inclusion of a double bond to an oxygen atom. Carbon compounds and moieties and their tautomeric forms. Examples of the moiety containing a carbonyl group include an aldehyde, a ketone, a carboxylic acid, a decylamine, an ester, an anhydride, and the like. The term "carboxy moiety or carbonyl moiety" refers to a group such as a "alkyl carbonyl group" wherein the alkyl group is covalently bonded to a carbonyl group;, an alkenylcarbonyl group; Wherein the alkenyl group is covalently bonded to the carbonyl group; "alkynylcarbonyl" group, wherein the alkynyl group is covalently bonded to the carbonyl group;, an arylcarbonyl group, Wherein the aryl group is covalently attached to the carbonyl group. Furthermore, the term also refers to a group in which one or more heteroatoms are covalently bonded to a carbonyl moiety. For example, the term includes the following individual moieties: for example, an amine carbonyl moiety (wherein the nitrogen atom is bonded to a carbon of a carbonyl group, for example, a decylamine); an amine carbonyloxy moiety, wherein the oxygen And both of the nitrogen atoms are carbon bonded to the carbonyl group (for example, also known as "urethane"). Further, an aminocarbonylamino group (e.g., urea) also includes other combinations of carbonyl groups bonded to a hetero atom (e.g., nitrogen, oxygen, sulfur, etc., and a carbon atom). Further, the hetero atom may be further substituted with one or more alkyl, alkenyl, alkynyl, aryl, 121012.doc •78-aralkyl, fluorenyl and the like. The term "thiocarbonyl" or "thiocarboxyl, a compound and moiety of a carbon containing a sulfur atom. The words are like parts of a few base parts. For example, the inclusion includes a double bond to the "thiocarbonyl moiety" includes a "thiocarbonyl moiety comprising an aminothio group wherein the amine group is bonded to the thio a carbon atom of a carbonyl group,

A carbon atom), an aminothiocarbonylamino group, and the like. The term "ether" includes a compound or moiety comprising an oxygen bonded to two different carbon or heteroatoms. For example, the term includes "alkoxyalkyl" which refers to covalent bonding to oxygen An atom and the oxygen atom is covalently bonded to an alkyl, alkenyl or alkynyl group of the other alkyl group. The term "vinegar" includes compounds and moieties comprising a carbon or heteroatom bonded to an oxygen atom and bonded to the carbonyl group. The term "brewed" includes alkoxycarboxy groups such as decyloxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butanylcarbonyl, pentoxycarbonyl, etc. The alkyl, alkenyl or alkynyl group. All are as defined above. The term "thioether" includes compounds and moieties comprising sulfur atoms bonded to two different carbon or heteroatoms. Examples of thioethers include, but are not limited to, alkylthioalkyl, alkane Thioalkenyl and alkylthioalkynyl. The term "alkylthioalkyl" includes an alkyl, alkenyl or alkynyl group having a bond to a sulfur atom and bonded to the alkyl group. Compound. Similarly, the term 'alkylenethioalkyl," and "alkylthio" are those in which an alkyl, alkenyl or alkynyl group is bonded to a sulfur atom and the sulfur atom is covalently bonded to A compound or moiety of an alkynyl group.

The term "hydroxy" or "hydroxyl, includes a group having _〇H 121012.doc •79-1342310 or -〇·. A π halogen includes fluorine, bromine, gas, Iodine, etc. The term "perhalogenated" usually refers to the part in which all hydrogen is replaced by a self-atomic atom. The term "polycyclic group" or "polycyclic group" includes two or more a portion of a plurality of rings (eg, 'cycloalkyl, cycloalkyl, cyclo, aryl, and/or heterocyclyl)' wherein two or more carbons are shared by two adjacent rings, for example 5, The ring system "fused ring" is referred to as a ring connected by a non-contiguous atom, a bridged ring. Each of the rings of the plurality of rings may be substituted by such substituents as described above, for example , for example, dentate, hydroxy, alkylcarbonyloxy, aryloxy, fluorenyl, aryloxyoxy, (tetra), thiol, & reduced, serotonyl amine Alkyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxy Base, phosphate, phosphonate, phosphinate, cyano, amine (including alkylamino, dialkylamino, arylamino, diarylamine and alkylarylamine) 'Hydrazinylamino (including alkylcarbonylamino, arylcarbonylamino, aminemethanyl and ureido), fluorenyl, imido, fluorenyl, alkylthio, arylthio, thiocarboxylate , sulfate group, alkylsulfinyl, sulfonate, sulfonamide, sulfonylamino, nitro, trifluoromethyl, cyano, azide, heterocyclic, alkyl, alkyl a group, or an aromatic or heteroaromatic moiety. The term "heteroatom" includes atoms other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulfur, and phosphorus. Combination " means that any number of the listed functional groups and molecules can be combined to give a larger molecular structure. For example, I2I012.doc * 80 - 1342310 The term "phenyl", "quot; carbonyl, (or "=〇,,), "-〇' ·,-0Η*, and C〗 6 (ie, _CH3 and -CH2CH2CH2-) can be combined to form 3-曱Substituted 4-propoxybenzoic acid substituents. It should be understood that when functional groups and molecules are combined to produce a larger molecular structure, hydrogen can be removed or added as needed to saturate the valence of each atom. All of the compounds of the present invention described above will further include, as needed, a bond between adjacent atoms and/or hydrogen to saturate the valence of each atom. That is, 'add a bond and/or a hydrogen atom to the following number • The total bond of the quantity is supplied to each of the following types of atoms: carbon: four bonds; nitrogen: three bonds; 氡: two bonds; and sulfur: two to six bonds

It should be noted that the structures of certain compounds of the invention include asymmetric carbon atoms. Therefore, we should be aware of the isomers produced by this asymmetry (for example, all enantiomers, stereoisomers, rotamers, tautomers, diastereomers or exosomes) Spiral) is included within the scope of the invention. Such isomers can be obtained in a substantially pure form by classical separation techniques and by stereochemically controlled synthesis. In addition, the structure and other compounds and parts of the case are also included in all tautomers. The compounds described herein are available through industry recognized synthetic strategies. . It should also be noted that the substituents of certain compounds of the invention include isomeric cyclic structures. Therefore, it should be understood that the individual isomers of the specific substituents are included in the scope of the invention unless otherwise stated. For example, the term "four 啥" includes four vomits, 2//. four saliva, three 仏 four 啥, four bites, and 5//- four vomits. 21012 d〇C -8, - 1342310 Uses The compounds of the invention have valuable pharmacological properties and are useful in the treatment of diseases.In certain embodiments, the compounds of the invention are used to treat bacterial infections. The term ''uses'' includes any one or more of the following examples of the invention, respectively The use of a pharmaceutical composition for the treatment of such diseases (for example, in the manufacture of a medicament); the use of a compound of the invention in the treatment of such diseases; the use of a compound of the invention for the treatment of Pharmaceutical preparations of such diseases; and compounds of the invention for use in the treatment of such diseases; where appropriate and advantageous, unless otherwise stated. In particular, the diseases to be treated and thus preferred for the use of the compounds of the invention are selected from bacterial infections and those diseases which depend on EF-Tu activity. The term "use" further includes embodiments of the compositions herein, which are sufficiently bonded to white for use as a tracer or marker for coupling to a fluorescent agent or label or becoming radioactive. It can be used as a research reagent or as a diagnostic or developer. In certain embodiments, the compounds of the invention are used to treat a disease associated with EF_Tu, and the compounds of the invention are used as any one or more

Inhibitor of Tu protein. One person is expected to be a therapeutic agent for inhibiting one or more EF-Tu isoforms. Analysis The inhibition of antibacterial activity by the compounds of the invention can be measured by the majority of assays available in the field. An example of this analysis is based on the standard minimum inhibitor concentration (MIC) test performed by the guidelines. 'Meal drug grades I210l2.doc, 82 · 1342310 The "effective amount" of the compound used is necessary or sufficient to treat or The amount of bacterial infection is prevented 'for example, to prevent various morphological and physical symptoms of bacterial infection, and/or the diseases or conditions described herein. In one example, the effective amount of the compound of the invention is sufficient to treat the bacterial infection in an individual. An effective amount may vary depending on factors such as individual size and body weight, type of disease, or a particular compound of the invention. For example, the choice of a compound of the invention may affect the composition of "effective amount". The factors contained herein can be studied and the determination of the effective amount of the compound of the present invention can be made without undue experimentation. It can be a concentrated 'main. In addition, 'the agent I of the compound according to the urgency of the treatment or prevention situation It can be increased or decreased proportionally. The compound of the present invention can be used for; a · bottom l + ~ ^ for & treatment as described herein, disease, disease Symptom or disease

The investment scheme can affect the composition of the effective amount. The compounds of the invention may be administered to an individual at or after the start of the bacterial sensation. In addition, several divided doses and staggered doses may be administered daily or sequentially, or the dose may be infused continuously, or may be used to make a pharmaceutical composition for the treatment of such diseases. The compound of the present invention is used to treat the ridiculous; the method of the disease, the disease of the temple, or the pharmaceutical preparation containing the compound of the present invention for treating the disease. A "pharmaceutical composition," comprising a agent suitable for administration to a mammal, such as a human. When the compound of the present invention is administered as a medicament to a mammal (e.g., human sputum 'which may be as it is or as, for example, 〇.1 to 99.5 〇/〇 (more preferably, 0.5 to 90%) active medicinal combination (d) h The phrase "pharmaceutically acceptable carrier" is used in the art and is recognized in the art and includes suitable compounds 121012, doc-83-1342310 to administer a compound of the invention to a compound or medium. The pharmaceutically acceptable materials, group excipients, solvents or sealants, liquid or solid fillers, diluents, or part of the body are carried or transferred to another target agent by - organ and blending Other ingredients are compatible = s 3 other part of the body. It must be "acceptable". In the sense of harm to the patient, examples of per-carrier materials include: Congzhi is pharmaceutically acceptable. The carrier materials such as corn temple powder and horse bells are sugar, glucose and sugar; temple powder, sodium sulfonate sodium, ethyl sensitizers such as rebel buds, alum, and, Cellulose acetate; powdered sulfonate gum; malt, gelatin, talcum powder. Such as m such as cocoa butter and suppository 蠛; oils, such as chemical oil, cotton cup, ^, /,, chemical oil, sesame oil, olive oil, jade oil and denier oil, diol cat a. Such as propylene glycol; Alcohols such as glycerin, sorbitol, mannitol and lauric acid vinegar H buffer ' 'such as oleic acid vinegar and 曰 曰, buffers such as magnesium hydroxide and hydroxide; sea lacquer 无; Heat source water; isotonic saline; Ringer's solution solution; ethanol; Phosphate Phosphate buffer solution; and other non-toxic compatible substances used in pharmaceutical formulations. Wetting agents, emulsifiers and lubricants ( For example, sodium lauryl sulfate and stearic acid (five) as well as coloring agents, release agents, coating agents, sweeteners, dwarfing agents and flavoring agents, preservatives and antioxidants may also be present in such compositions. Examples of acceptable antioxidants include: water-soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium sulphate, sodium metabisulfite: sodium sulfite, and the like; oil-soluble antioxidants such as Blood ester, butylated hydroxyanisole BHA), butylated hydroxytoluene 1210I2.doc -84- 1342310 (ΒΗΤ), egg fat 'propyl gallate' alpha tocopherol, and the like; and metal chelating agents such as citric acid, ethylenediamine Tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. The formulations of the present invention include those suitable for oral, nasal, topical, buccal, sublingual, rectal, vaginal and/or parenteral administration. Isoforms may conveniently be presented in unit dosage form and may be prepared by any methods well known in the pharmaceutical art. The amount of active ingredient which may be combined with the carrier materials to produce a separate dosage form will generally be the amount of the compound which produces a therapeutic effect. In general, the amount of active ingredient may range from about 1% to about 99%, preferably from about 5% to about 70%, optimally from about 10% to about 30%, in addition to 100°/❶. Methods of preparing such formulations or compositions include the step of bringing into association a compound of the invention with a carrier and, optionally, one or more accessory ingredients. In general, the ’'s meta-equivalent formulation is prepared by uniformly and thoroughly mixing the compound of the present invention with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product. The formulations of the present invention suitable for oral administration may be in the form of capsules, cachets, pills, lozenges, lozenges (using a flavoring base, usually sucrose and gum arabic or sulphonate), powders, granules Or as a solution or suspension in an aqueous or non-aqueous liquid: either as an oil-in-water or water-in-oil liquid emulsion; or as an elixir or syrup; or as a soft lozenge (using an inert substrate, for example Gelatin and glycerin, or sucrose and gum arabic) and/or as mouthwashes and the like, each comprise a predetermined amount of a compound of the invention as an active ingredient. The compounds of the invention may also be administered as a bolus, paper or paste. 12l012.doc -85. In the solid dosage form (capsules, granules, pills, dragees, powders, granules and the like) of the present invention for oral administration, the active ingredient tr and one or more pharmaceutically acceptable substances A carrier (such as sodium citrate or hydrogen phosphate dance) and/or any of the following ingredients: a filler or extender such as powder, lactose, sucrose, glucose, mannitol and/or citric acid; (for example) carboxymethyl cellulose, alginate, gelatin, polyethylene 0 to 11 ketones, sucrose and/or gum arabic; humectants such as glycerin; disintegrants such as agar, calcium carbonate, potato Or tapioca starch, alginic acid, certain citrates and sodium carbonate; solution retarders such as paraffin; absorption accelerators such as the fourth ammonium compound; wetting agents such as, for example, cetyl alcohol and glycerol Monostearate; absorbents such as kaolin and bentonite; lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof; and color formers. In the case of capsules, binders and pills, the pharmaceutical compositions may also include buffering agents. Solid and similar types of solid compositions can also be used as fillers in soft and hard-filled gelatin capsules such as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. Tablets may be prepared by compression or molding, optionally containing - or a plurality of adjuvant ingredients. For the compressed tablets, a binder (for example, gelatin or hydroxypropylmethylcellulose), a moisturizing agent (iv), an inert diluent, a control solution (for example, sodium acetate acetate or crosslinked methylcellulose) can be used. Prepared with a surfactant or a dispersing agent. Molded tablets may be prepared by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. Tablets and other solid dosage forms of the pharmaceutical compositions of the present invention (e.g., dragees 121012.doc-86*, capsules, pills, and granules) may optionally be scored or used in packages such as enteric mash and other pharmaceutical formulation techniques.臈 and other envelope and shell preparation. It is also possible to formulate, for example, hydroxymethylcellulose, other polymer matrices, liposomes and/or microspheres in varying proportions to provide the desired release profile for providing slow or controlled release of the active ingredient therein. The solid dosage forms can be sterilized by, for example, filtration through a bacterial retention filter, by incorporation of a bactericidal agent, which can be used just prior to use; ',', bacterial water or some other sterile injectable A sterile solid composition in the form of a medium. The composition may also optionally contain an opacifying agent and, where appropriate, a composition which is active (or preferentially) in a portion of the gastrointestinal tract. Examples of useful embedding compositions include polymers and waxes. Suitably, the/tongue component may also be in the form of a microcapsule containing one or more of the above excipients. Liquid dosage forms for oral administration of the compounds of the present invention include pharmaceutically acceptable remedies, microemulsions, solutions, suspensions, syrups and elixirs. These liquid dosage forms may contain, in addition to the active ingredient, inert diluents conventionally employed in the art, such as, for example, water or other solvents, solubilizers and emulsifiers, for example, ethanol, isopropanol, ethyl carbonate, Ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, oil (specifically, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerin, Tetrahydrofuranol, polyethylene glycol, and sorbitan fatty acid esters, and mixtures thereof. Besides the inert diluent, the oral compositions may also include adjuvants, for example, wetting agents, emulsifying and suspending agents, sweetening agents, flavoring agents, coloring 121012.doc • 87· 1342310, flavoring agents And preservatives. In addition to the active compound, the suspension also contains suspending agents such as, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, hydrogen partial hydrogen. Alumina, bentonite, agar and sulfonamide and mixtures thereof.

Formulations of the pharmaceutical compositions of the present invention for rectal or vaginal administration may be presented in the form of a suppository, which may be prepared by admixing the compound or compounds of the present invention with one or more suitable non-irritating excipients or carriers. Such non-irritating excipients or carriers include, for example, cocoa butter, polyethylene glycol, suppository wax or salicylate, and which are solid at room temperature but liquid at body temperature and therefore will The active compound is dissolved and released in the rectum or vaginal cavity. Formulations of the invention suitable for vaginal administration also include pessaries, vaginal plugs, creams, gels, pastes, foams or spray formulations containing such carriers as are conventionally known in the art.

Dosage forms for topical or transdermal administration of the compounds of the present invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compound can be mixed under sterile conditions with apharmaceutically acceptable carrier and any preservative, buffer or propellant which may be required. Such ointments, pastes, creams and gels may contain excipients such as animal and fats, oils, waxes, paraffin polyethylene glycols, polyfluorene oxides, swollen starches, sulphur. Silicone, cellulose derivative soil, acid, talc and zinc oxide or a mixture thereof. In addition to the compound of the present invention, the powder and the spray may contain excipients, such as lactose (7), Shi's private, argon, arsenic, and arsenic powder 121012.doc -88· 1342310 or Mixtures of other materials> Sprays may additionally contain conventional propellants such as fluorocarbons and volatile unsubstituted hydrocarbons such as butane and propane. Transdermal patches have the added advantage of providing controlled delivery of the compounds of the invention to the body. Such dosage forms can be prepared by dissolving or dispersing the compound in a suitable medium. Absorption enhancers can also be used to increase the rate at which the compound melts through the skin. The rate of this flow can be controlled by providing a rate controlling membrane or dispersing the active compound in a polymer matrix or gel. Ophthalmic formulations, ophthalmic ointments, powders, solutions and the like are also encompassed within the scope of the invention. Pharmaceutical compositions of the present invention suitable for parenteral administration comprise one or more compounds of the invention together with one or more pharmaceutically acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders The sterile powders may be reconstituted as a sterile injectable solution or dispersion before use. The pharmaceutical compositions may contain antioxidants, buffers, bacteriostatic agents, and may render the formulation isotonic with the blood of the intended recipient. Solute or suspending agent or enhancer. Examples of suitable aqueous and non-aqueous vehicles which may be used in the pharmaceutical compositions of the present invention include water, ethanol, polyols (e.g., glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils (e.g., olive oil), and Injectable organic esters (e.g., ethyl oleate suitable flowability can be maintained, for example, by the use of coating materials such as lecithin, in the case of dispersions, by maintaining the desired particle size, and by using surface actives The compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. The prevention of microbial action can be ensured by the introduction of various antibacterial agents and 121012.doc •89-1342310 antifungal agents. For example, p-hydroxybenzoic acid, butyl alcohol, phenol sorbic acid, and the like. It is also desirable to include such agents in such compositions, such as riding, gasification, and the like. : Absorbing agents (eg, aluminum monostearate and gelatin) provide long-lasting absorption in injectable pharmaceutical forms.

In some cases, in order to prolong the efficacy of the drug, it is necessary to slow the absorption of the drug from subcutaneous or intramuscular injection. (d) by means of a liquid suspension of a crystalline or amorphous material having a poor water solubility. Thus, drug absorption 2: depends on its dissolution rate, and the dissolution rate depends on the crystal size and crystal form. Alternatively, delayed absorption of the drug form can be achieved by dissolving or suspending the parenterally administered drug in an oil vehicle. The injectable storage form is prepared by forming a microcapsule matrix of the target compound in a biodegradable polymer such as polyacetamide-polyglycolic acid. Looking at the ratio of drug to polymer and the properties of the particular polymer used,

The rate of drug release can be controlled. Examples of other biodegradable polymers include poly(original 驮s曰) and poly(anhydride). Formulations for injectable injections can also be prepared by coating the drug with a liposome or microemulsion which is compatible with body tissues. The formulations of the invention may be administered orally, parenterally, topically or rectally. Of course, the genus is given in a form suitable for each administration route. For example, such systems, lozenges or capsules are administered by injection, inhalation, by injection, infusion or inhalation in the form of eye lotions, ointments, suppositories, and the like; in the form of lotions or ointments. And rectal administration in the form of suppositories. Oral and/or IV administration is preferred. In this article, the phrase "parenteral administration" and "administered parenterally" means 121012.doc 1342310, except for enteral and topical administration, usually by injection, and Including (but not limited to) intravenous, intramuscular, intraarterial, intrathecal, transcapsular beta, transforaminal, intracardiac, intradermal, transperitoneal, transtracheal, subcutaneous, Subcutaneous, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal injections and infusions. The phrase "full body administration" is used in this article, "subject to systemic administration", &quot;&quot;and&quot;in the form of terminal administration&quot; means to inject a compound, drug, or other material differently from the direct entry into the middle-framed nervous system, to allow it to enter the patient's body and thereby undergo metabolism and other similar The procedure, for example, is administered subcutaneously. The compounds can be administered to humans and other animals for treatment by any suitable route of administration, including oral, nasal (e.g., in the form of, for example, a spray), transrectal, transvaginal. Internal, parenteral, intracerebroventricular and including oral and sublingual parts (eg in the form of powders, ointments or drops). </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> <RTIgt; Dosage form. The actual dosage level of the active ingredient in the pharmaceutical compositions of the present invention can be varied to achieve an amount of effective active ingredient that is not toxic to a particular patient, composition, and mode of administration to achieve the desired therapeutic response. . The dosage level will be determined by a variety of factors, including the particular compound of the invention or its activity, salt or acetonide activity, route of administration, administration of pg^*, B, specific compounds used. Excretion rate, duration of treatment 121012.doc 1342310, other drugs, compounds and/or materials used in combination with the specific compound used, age, sex, weight, physical condition, health status and prior medical history of the patient to be treated and already in medicine Similar factors well known in the art. A physician or veterinarian who is familiar with the art can readily determine the effective amount of the desired pharmaceutical composition and prescribe it. For example, a physician or veterinarian can begin doses of the compounds of the invention used in a pharmaceutical composition below the level desired to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In general, a suitable daily dose of a compound of the invention is the amount of the compound which is effective to produce the lowest dose of the therapeutic effect. This effective dose will generally depend on various factors as described above. Generally, the intravenous and subcutaneous dosages of the compounds of the invention will range from about 1 to about 100 mg/kg body weight per day, more preferably from about 1 to about 100 mg/kg body weight, for a patient to be used to indicate an analgesic effect. 50 mg / kg / day ' and still better about 1.0 to about 1 mg / kg / day. An effective amount is the amount of bacterial infection treated. If an &apos;effective sputum dose of the active compound is desired, it can be administered as a unit dosage form at intervals of 2, 3, 4, 5, 6 or more divided doses administered at appropriate intervals. For the compound of the present invention, although it can be administered alone, it is preferred to administer the compound as a pharmaceutical composition. Synthetic Sequences The compounds of the present invention are prepared from commonly available compounds using procedures well known to those skilled in the art, including but not limited to any one or more of the following conditions: 121012.doc • 92· 1342310

Within the scope of this document, unless otherwise stated by the context, only groups which are not intended to be the final product of the present invention and which are readily removable are referred to as &quot;protecting groups&quot;. The protecting of the functional groups by the protecting groups, the protecting groups themselves and their removal reactions are described, for example, in standard reference documents such as, for example, Science of Synthesis: Houben-Weyl Methods of Molecular Transformation. Georg Thieme Verlag, Stuttgart, Germany. 2005. % 41627 I (URL: http ://www.science-of-synthesis, com (Electronic Version, Volume 48)); JFW McOmie's 'Protective Groups in Organic Chemistry&quot *Plenum Press, London and New York 1973, 'In TW Greene and PGM Wuts&quot;Protective Groups in Organic Synthesis&quot;, 3rd edition, Wiley, New York 1999, in &quot;The Peptides&quot; Volume 3 (Editor :E. Gross and J_ Meienhofer), Academic Press, London and New York 1981, in &quot;Methoden der organischen Chemie&quot; {Methods of Orgawfc Houben Weyl, 4th edition, Vol. 15/1,

Georg Thieme Verlag, Stuttgart 1974, in H.-D. Jakubke and H. Jeschkeit &quot;AminosSuren, Peptide, Proteine&quot; acids, Peptides, Proteins), Verlag Chemie, Weinheim, Deerfield Beach and Basel 1982 and described in Jochen Lehmann's &quot;Chemie der Kohlenhydrate: Monosaccharide und Derivate&quot; {Chemistry of Carbohydrates: Monosaccharides and

Derz’vaiz’ves), Georg Thieme Verlag, Stuttgart 1974. The protective group is characterized in that it can be easily removed (for example, by solvolysis, reduction, photolysis by 12I012.doc -93· 1342310 or under physiological conditions (for example, by enzymatic cleavage) Undesired side reaction). Salts of the compounds of the invention having at least one salt forming group can be prepared in a manner known per se. For example, a salt of a compound of the present invention having an acid group can be formed, for example, by using a metal compound (for example, a metal salt suitable for organic slow-working, such as a sodium salt of ethyl 2-hexanoate). Using an organic test metal or a soil metal compound (for example, a corresponding hydroxide, carbonate or bicarbonate such as a sodium or potassium hydroxide, carbonate or argon carbonate), with a corresponding compound or ammonia Alternatively, the compounds may be treated with an organic amine, preferably using a stoichiometric or only slightly excess salt forming reagent. The acid addition salts of the compounds of the invention are obtained in a conventional manner, for example, by treatment with an acid or a suitable anion exchange reagent. For example, an internal salt of a compound of the invention containing an acid and a base salt forming group (eg, a free carboxyl group and a free amine group) can be neutralized, for example, by a weak base, for example, by acid addition. Salt) to isoelectric point or formed by treatment with an ion exchanger. The salt can be converted to the free compound in a conventional manner; the metal and the money salt can be converted, for example, by treatment with a suitable acid, and the acid addition salt can be converted, for example, by treatment with a suitable reagent. Mixtures of isomers obtainable according to the invention may be separated into individual isomers in a manner known per se; diastereomers may be partitioned, for example, between heterogeneous solvent mixtures, Recrystallization and/or chromatographic separation (for example, by gelatin or by, for example, medium pressure liquid chromatography through a reverse phase column), and the racemate can be formed, for example, with an optically pure salt. Forming a salt and isolating the mixture of diastereomers thus obtained (for example, by 121012, d〇c-94- assisting in fractional crystallization or separation of the mountains. 3 chromatography through optically active column material) can be classified according to the standard The method (彳丨... uses a chromatographic method, a distribution method, (re), ', 〇aa, and ^u such a frequency, a mother 4*. The intermediate and the final product are treated and/or purified as a general process condition. The procedures applicable to the entire disclosure of the present invention are applicable. The process steps for synthesizing the compounds of the present invention can be carried out under the reaction conditions known per se, and the conditions include those described by Zhao. Agent does not exist In general, such solvents or diluents include, for example, a solvent or diluent which is inert to the reagents employed and which dissolves them; in a catalyst, a condensing agent or a neutralizing agent (for example, an ion exchanger, such as a cation exchanger, For example, in the form of ruthenium, depending on the nature of the reaction and/or reactants) in the absence or presence; at low temperatures, normal temperatures or elevated temperatures (eg, temperatures ranging from about -100 ° C to about 190 * t) Between, for example, about 8 (Γ (: to about 15 ° ° C ' for example at -80 to -6 〇 t, at room temperature, at -20 to 40 ° C or at reflux temperature Under normal pressure or in a closed vessel, wherein the vessel is under suitable pressure and/or in an inert atmosphere, such as under an argon or nitrogen atmosphere. At all stages of the reaction, isoforms are formed. The mixture can be separated into individual isomers (eg, diastereomers or enantiomers) or separated into any desired mixture of isomers (eg, racemate or non-pair) a mixture of molecules, for example, similar to Science of 121012.doc -95- 1342310

Synthesis: Houben-Weyl Methods of Molecular

Transformation. Georg Thieme Verlag, Stuttgart, Germany 2005 method. Unless otherwise stated in the description of such processes, solvents which may be selected for their particular solvent may include, among other things, specifically, or, for example, water, esters (eg, lower alkyl) _ lower carbon number alkanoates, such as ethyl acetate), ethers (such as aliphatic ethers, such as diethyl ether) or cyclic ethers (such as tetrahydrofuran or dioxane), liquid aromatic hydrocarbons (such as benzene) Or benzene), alcohol (such as decyl alcohol, ethanol or hydrazine or 2-propanol), nitrile (such as acetonitrile), southern hydrocarbon (such as di-methane or gas), decylamine (such as dimethyl decylamine) Or dimethylacetamide), a base (such as a heterocyclic nitrogen base such as pyridine or methylpyrrolidine-2-one), a carboxylic anhydride (such as a lower carbon number alkanoic anhydride such as acetic anhydride), known, a direct or branched hydrocarbon (eg, cyclohexane, hexyl or isopentane) or a mixture of such solvents (eg, an aqueous solution). These solvent mixtures can also be used in the treatment by, for example, chromatography or partitioning. The compounds (including salts thereof) may also be obtained in the form of a hydrate, or the crystal thereof may, for example, include a solvent for crystallization. Different crystal forms may be present. The invention also relates to the form of the following process: the towel is used as an intermediate in any stage of the process as a starting (four) and the process step is carried out or wherein the starting material is formed under the reaction conditions or The form of the derivative (for example, in protected form or in the form of a salt) or the compound obtained by the process of the invention is produced under process conditions and further processed in situ. Prodrugs I21012.doc • 96 - 1342310 The invention also encompasses pharmaceutical compositions comprising a pharmaceutically acceptable prodrug compound of a compound of the invention and a method of treating a bacterial infection via administration of a pharmaceutically acceptable prodrug compound of the compound of the invention. For example, a compound of the invention having a free amine group, a guanamine group, a hydroxyl group or a carboxyl group can be converted into a prodrug. Prodrugs include a polypeptide chain in which an amino acid residue or two or more (eg, two, three or four) amino acid residues are covalently linked to a compound of the invention via a guanamine or ester linkage a compound of a free amine, hydroxyl or carboxylic acid group. The amino acid residues include, but are not limited to, two naturally occurring amino acids, usually named by three letter symbols, and also include 4-hydroxyproline, hydroxy lysine, alpha-chain, and iso-chain , 3-methylhistamine, n-proline, β-alanine, γ-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine and bismuth methionate. Other types of prodrugs are also covered. For example, a free carboxyl group can be derivatized to a guanamine or an alkyl ester. The use of, but not limited to, a hemisuccinate, a phosphate, a dimethylamino acetate, and a phosphorus methoxy methoxycarbonyl group can be used. The free hydroxyl group derived from the group within is described in Advanced Drug Delivery Reviews, 1996, 19, 115. Amino acid ester prodrugs of hydroxyl and amine groups, such as carbonate prodrugs, sulfonates and sulfates, are also included. The invention also contemplates the derivatization of a hydroxy group to (nonoxy)methyl ether and (decyloxy)ether, wherein the thiol group can optionally include, but is not limited to, ether, amine, and carboxylic acid functional groups. An alkyl ester substituted with a group within or a carboxylic acid ester thereof wherein the thiol group is as described above. Prodrugs of this type are described in j. Med. Chem. 1996, 39, 10. The free amine can also be derivatized as a guanamine, sulfonamide or phosphoniumamine. All of these prodrug moieties can include various groups including, but not limited to, ether, amine, and carboxylic acid functional groups within 121012.doc • 97-. Thus, where appropriate and convenient, any reference to a compound of the invention is to be understood as referring to a corresponding prodrug of a compound of the invention. Redness The compounds of the invention may also be used in combination with other agents (e.g., other antibacterial compounds that are or are not a compound of the invention) for the treatment of bacterial infections in an individual. The term "combination" means a fixed combination in the form of a dosage unit or a combination of components for administration (wherein the compounds and combinations of the invention can be administered simultaneously or separately at intervals) The time intervals in particular allow the combination components to exhibit a synergistic effect (eg, synergy h, or any combination thereof. The compounds of the invention may be used in combination with another antibacterial agent. The term &quot;antibacterial agent, means having Bactericidal or bacteriostatic is any substance that kills or inhibits the growth of bacterial cells. Antibacterial agents include antibiotics, biocides, antimicrobials, and bacteriostatic agents. These known types of antibiotics include, for example, cell wall synthesis inhibition. Agents, cell membrane inhibitors, protein synthesis inhibitors, and inhibitors that bind to DNA or RNA or affect DNA or RNA synthesis. Most antibiotic agents suitable for use in the treatment of diseases and conditions associated with bacteria have been known and disclosed, for example, in (eg) The Physician's Desk Reference (PDR), Medical Economics (Montvale, NJ), (53rd edition), 1999;

Mayo Medical Center Formulary, Unabridged Version, Mayo Clinic (Rochester, Minn.), January 1998; Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals, (I21012.doc -98 · 1342310 11th edition), Merck &amp; Co., Inc. (Rahway, NJ), 1989; University of Wisconsin Antimicrobial Use Guide, http://www.medsch.wisc.edu/clinsci/ 5amcg/amcg.html;

Introduction on the Use of the Antibiotics Guideline, of Specific Antibiotic Classes, Thomas Jefferson University, http://jeffiine.tju.edu/CWIS/OAC/Antibiotics_guide/intro.html and in the literature described therein.

Examples of antibiotics for use in combination with the compounds of the invention include, but are not limited to, quinolone, macrolide, glycopeptide, stagnation, beta-enhanced amine ( Including amoxicillin, ampicillin, bacampicillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, Methillillin, mezlocillin, nafcillin, benzene, oxacillin, penicillin G, penicillin V, piperacillin, piazcillin Pivampicillin), pemmecillinam, ticarcillin, sulbactam, tazobactam, clavulanate, cephalosporin Cefaclor), cefdroxil, cefmandole, cefazolin, cefdinir, cefditoren, cefepime ,head Ceflxime, cefonicid, cefoperazone, cephalosporin 121012.doc -99- 1342310

(cefotaxime), cefotetan (cefotetan), cefoxitin, cefp〇d〇xinie, cefprozil, ceftazidime, ceftibuten ), head holding "ceftizoxime", ceftriaxone, cefuroxime, cephalexin, cephal〇thin, cephapirin , cephradine, aminoglycosides (including gentamycin, streptomycin, amikacin, kanamycin, viomycin) ), capreomycin, ethionamide, prothionamide, cycloserine, dapsone, clofazimine , tetracyclines (tetracycline, doxycycline, chlortetracycline, oxytetracycline, minocycline, demeclocycline), ° Evil vomiting ketones (Lina 0 sitting (Linezolid), by slightly ° dioxanone (eperezolid)), Xiao Yue stone laugh (metronidazole), rifabutin (rifabutin), isoniazonid, ethambutol (ethambutol), and combinations thereof. Examples of antiviral agents for use in combination with the compounds of the invention include, but are not limited to, zidovudine, lamivudine, didanosine, zalcitabine, Stavudine, abacavir, nevirapine, delavirdine, emtricitabine, efavirenz, saquinavir ), ritonavir 121012.doc -100- 1342310 (ritonavir), indinavir, nelfinavir, amprenavir, tenofovir, a Adefovir, atazanavir, fosamprenavir, urethrazine, AL-721, ampligen, butylated trans-toluene; polymannoacetate, chestnut Spermine

(castanospermine); contracan; creme pharmatex, CS-87, penciclovir, famciclovir, acyclovir, cytofovir, ganciclovir, dextran sulfate Sulfate), D-penicillamine, tri-nanoic acid, fusidic acid, HPA-23, eflornithine, nonoxynol, Isey Pentamidine isethionate, peptide T, phenytoin, isoniazid, ribavirin, rifabutin, ansamycin, trimethoate Trimetrexate, SK-81 8, suramin, UA001, enfuvirtide, by gp41

Derivatized peptide, CD4 antibody, soluble CD4, molecule comprising CD4, CD4-IgG2 and combinations thereof. Other examples of agents that can be used in combination with the compounds of the invention include, but are not limited to, free radical scavengers, ascorbic acid, vitamin C, anticancer agents, chemotherapeutic agents, non-steroidal anti-inflammatory drugs, steroid anti-inflammatory drugs, Antifungal agent, detoxifying agent, analgesic, bronchodilator, drug for treating local vascular deficiency, antibody single agent, minoxidil for topical application to hair growth, diuretic, immunosuppression Agents, lymphokyne, a- and -beta-interferons, and combinations thereof. 121012.doc •101 - Or hair: Compound and any other agent can be formulated in separate dosage forms. Other Agents The amount of the dosage form administered to the patient is small, and the compound of the present invention is formulated with any combination of any of the 'σ M groups. For example, the inhibitor of the present invention can be formulated in a dosage form which can be formulated together with another dosage form. Any separate dosage form can be administered simultaneously or at different times. Or the 'present composition of the invention includes other agents as described herein. Each of the wounds may be present as a separate composition, a combined composition, or in the form of a single composition. The invention is further illustrated by the following examples, which are not to be construed as limiting the invention. Unless otherwise indicated, the practice of the present invention will employ techniques commonly employed in cell biology, cell culture, molecular biology, transgenic biology, microbiology, and immunology, which are within the skill of the art. General Synthetic Methods All of the starting materials, structural units, reagents, acids, tests, dehydrating agents, solvents, and catalysts used to synthesize the compounds of the present invention may be constructed or may be organically known to those of ordinary skill in the art. Synthetic methods are produced (Houben Weyl^4^ « 1952, Methods of Organic Synthesis, Thieme, Vol. 21). Furthermore, the compounds of the present invention can be produced by an organic synthesis method as is conventionally known to those skilled in the art as shown in the following examples. Example Definition Acetic acid

AcOH 121012.doc •102- 1342310 aq Aqueous Boc ·Tri-butoxycarbonyl DMF N,N-dimethylformamide DCC Dicyclohexylcarbodiimide DCE Di-ethane ethane DCM Dioxane DMAP 4 - dimethylaminopyridine DMSO dimethyl sulfoxide EtO Ac ethyl acetate EtOH ethanol eq equivalent LC liquid chromatography LCMS liquid chromatography mass spectrometry MeOH methanol MHz dead Hertz PS polystyrene RT room temperature Rt retention time s solid sat. saturated TEA triethylamine TFA trifluoroacetic acid THF tetrahydro alpha futham h hour 121012.doc -103-min minute m/z mass/charge MS mass spectrometry HRMS high resolution mass spectrometry NMR NMR analysis Method NMR: Proton spectra were recorded on a Bruker 400 MHz uhrashield spectrum meter. Chemical shifts were recorded relative to methanol (δ 3.31), dimethyl sulfoxide (δ 2.50) or gas (δ 7 · 26). LCMS: Inerts ii 〇DS-3 column with a 2 minute gradient elution (25% acetonitrile / H2 〇 / 5 mM citric acid) and a flow rate of 4 ml / molecule (Cl 8, 50 X 4 · 6 mm The compound was analyzed on a 3 micron basis. HPLC purification was performed using a C8 or C18 column (30 X 1 mm, 5 μm, commercial: Sunfire or XTerra) and was performed according to two methods. Method 1% TFA consisted of 10%-95% ACN in water. Method 2 consisted of 1 mM mM NH4OH in 40%-95% ACN aqueous solution. LC analysis used a trademark Atlantis C18 tube (15 mm) with gradient elution (〇_95% aqueous acetonitrile + 〇 TFA). General Process 1 : 1210l2.doc -104- 1342310

The compounds of formula (1) may be prepared by synthetic methods well known to those skilled in the art or alternatively may be isolated from the fermentation broth. See, for example, U.S. Patent No. 5,202,241, which is incorporated herein in its entirety. The compound of the general formula (?) can be prepared from Process A by rearranging the compound (1) in water and suitably mediated by an acid or a base. The compound of the formula (iii) is prepared in process B t from (n) directly via reaction with azide or alternatively: a plurality of step processes comprising: removing by g or hydrolyzing The functional group is activated by a suitable activator, and is reacted with a suitable reagent (for example, azide). The azide represented by the formula G(1) is well known in the art and is easily used by the industry standard. Program synthesis. The compound of the formula (W) can be prepared by reacting an azide (Hi) with a nucleophilic agent, an alcohol, an amine or a propanol group (X1). Changi protecting groups can be selected by those skilled in the art. The protecting group is selected to be suitable for the conversion and can be removed by synthetic methods with little or no loss of yield. The introduction and selective removal of the protecting group is taught in Greene and Wake's Protective Groups in Organic Synthesis&quot; » John Wiley &amp; Sons (1991). The compound of the general formula (v) can be obtained by reacting the compound (iv) with a reagent (for example, an electrophile, an alkylating agent, a thiolation reagent or a sulfonium group (X2)) to obtain a compound (V). ) prepared. The compound of the general structure (VI) can be produced by reacting a compound with an acid, a base, a nucleophile or an electrophile to remove the protection (4) (X1). The compound of the general structure (vii) can be produced by reacting the compound (vi) with a suitable electrophile, an alkylating agent or a thiolation reagent (X3). The compound of the general structure (viii) can be produced by reacting the compound (vii) with an acid, a base, a nucleophile or an electrophile to remove the protective group (X2). Alternatively, any of the steps (A_G) may be performed in a different order, or some steps may be removed or slightly altered as will be apparent to those skilled in the art. Flowing private 2. Preparation of common intermediate b〇c-amine (4): 12l012.doc 1342310

Preparation of common intermediate (4):

Step 1-3' Preparation of azide nitrogen (2): 121012.doc -107- 1342310

Add 20 ml of hydrazine and NaOH (60 mg, 1.50 mmoles at 60 ° (:) to the solution of the ester (1, 1.5 g, ι. ΐό millimolar) in THF (300 mL). The reaction was stirred for 1.5 h and was monitored by TLC (10% MeOH / DCM) and LCMS. After the reaction was completed, concentrated to dryness. The off-white solid was suspended in sm. The dry state was repeated (3 times), whereby an off-white solid acid was obtained. The crude solid was stored in vacuo (1 Torr) for 12 hours. LCMS: Rt = 1.12 min, [M+H] + l 125. The crude acid was suspended in 300 ml of acetone. The flask was ultrasonicated and the solid on the side wall of the flask was lowered for 15 minutes. Add TEA to the suspension #2,0 ml, 14.2 mmol Ear) and gaseous ethyl formate (2.0 ml ' 20.91 mmol). The reaction appeared to dissolve slowly. Further ultrasonic treatment and use vigorous stirring to break up all the particles. After 1 hour, the reaction was carried out via 1^1^8 It seems to have been completed and added ^1^3 (500 mg, 7.69 mmol). The suspension was white at 60 ° C (appearance was white) /Yellow) Stir for 1 hour and monitor by LCMS. Add two additional portions of NaN3 (500 mg, 7.69 mmol) and stir the reaction for 20 min. The reaction was concentrated to EtOAc and flash chromatography (1.5WX 1.5&quot; SiO 2 column, 3 liters of EtOAc) was applied to 121012.doc -108 - 1342310. Purification afforded 920 mg of crude thiol-azide (2) as a white solid. In the next step without further purification. LCMS: Rt = 1.55 min, [M+H] + l 150. Step 4. Preparation in Boc-amine (3):

A suspension of thiol-azide (2,920 mg) was heated in a third-BuOH (1 gram) (80 ° C). Complete dissolution occurred after 2 hours and the reaction appeared to have been completed by LCMS after 12 hours. The solution was concentrated directly onto Si 2 and chromatographed (gradient elution: 50-70% EtOAc/hexanes) to give 600 mg of Boc-amine (3) as a white solid. 4 NMR (400 MHz, #^-DMSO) δ 10.38 (br s, 1 Η), 9.00 (d, 1 Η), 8.70 (app d, 2 H), 8.58 (s, 1 H), 8.44-8.41 ( m, 1 H), 8.38 (d, 1 H), 8.23 (s, 1 H), 8.11 (d, 1 H), 7.48 (br s, 1 H), 7.38-7.23 (m, 7 H), 6.02 (br s, 1 H), 5.31-5.18 (m, 3 H), 5.01-5.00 (m, 1 H), 4.97 (s, 2 H), 4.30-4.24 (dd, 1 H), 3.79 (dd, 1 H), 3.38 (s, 3 H), 2.75-2.68 (m, 1 H), 2.47 (d, 3 H), 2.22-2.13 (m, 1 H), 1.49 (s, 9 H), 1.37- 1.31 (m, 1 H), 0.87 (d, 3 H), 0.84 (d, 3 H). LCMS: Rt = 1.72 min. [M+H] +1196. •109- 121012.doc

I Step 5, Preparation of Boc#-acetate (4):

To the solution of the Boc-amine (3,540 mg, 0.451 mmol) in DCM (250 mL) was added acetic anhydride (0.100 mL, 0.979 mmol), pyridine (1.0 mL, 12.4 mmol) And DMAP (20 mg, 0.169 mmol). The reaction was stirred for 3 h, concentrated directly to EtOAc and EtOAc (EtOAc:EtOAc:EtOAc 4 NMR (400 MHz, A-DMSO) δ 10.38 (br s, 1 Η), 9.20 (br d, 1 H), 8.79 (br d, 1 H), 8.61 (br d, 1 H), 8.56 (s , 1 H), 8.44-8.41 (m, 1 H), 8.38 (d, 1 H), 8.24 (s, lH), 8, ll (d, lH), 7'48 (brs, lH), 7_42 ( s, 2H), 7.35-7.29 (m, 6 H), 6.14 (s, 1 H), 5.47 (t, 1 H)} 5.31-5.26 (m, 1 H), 5.19 (dd, 1 H), 4.97 (s, 3 H), 4.26 (dd, 1 H), 3.72 (dd, 1 H), 3.38 (s, 3 H), 2.70-2.65 (m, 1 H), 2.59 (s, 3 H), 2.45 (d, 3 H), 2.22-2.14 (m, 1 H), 1.96 (s, 3 H), 1.57-1.50 (m, 1 H), 1.49 (s, 9 H), 0.88 (d, 3 H) , 0, 84 (d, 3 H). LCMS: Rt = 1.81 min, [M+H] + 1238. Example 1, Preparation of Indoleamine (5) · 121012.doc -110- 1342310

To the solution of the Boc-amine (3,10 mg, 0.0083 mmol) in DCM (10 mL) was added TFA (1 mL, 13.46 mmol). concentrate. The resulting yellow foam was dissolved in DCM (10 mL) and concentrated (3 times). The crude amine salt was used directly without further purification. LCMS: Rt = 1.33 min, [M+H] +1 s. To a solution of this amine (0.0083 mmol) in pyridine (1 mL) was added ethyl acetate (0·100 mL, 0.979 mmol). The solution was stirred at room temperature for 1 minute and poured into a saturated aqueous solution of sodium hydrogencarbonate (100 mL). The mixture was extracted with EtOAc (3x) and dried with EtOAc EtOAc. The crude product was purified by flash chromatography ( gradient elution: 0-5% MeOH / DCM) to afford 6 mg of decylamine (5) as white solid. 'H NMR (400 MHz, A-DMSO) 5 11 14 (br s, 1 Η), 9.00 (br d, 1 Η), 8.68-8.66 (m, 2 Η), 8.59 (si H) 8.45-8.42 ( m, 1 H), 8, 40 (d, 1 H), 8.24 (s, 1 h), 8.13 (d ! H), 7.80 (s, 1 H), 7.38-7.21 (m, 7 H), 6.01 (br d &gt; χ H) 5.32-5.17 (m, 3 H), 5, 01-4.99 (m, 1 H), 4.97 (s, 2 H) 4 27 (dd, 1 H), 3.79 (dd, 1 H), 3.38 (s, 3 H), 2.73-2.68 (m,! H) -Ill ^ 121012.doc 1342310 2_46 (d,3 H), 2.19-2.14 (work, j H) (m,1 H) , 0.87 (d, 3 H), 0.84 (heart 3, 2.10 (s, 3 H), 1.35-1.28 clock, [M+H] + 11 38. [CMS · Rt _ 1.35 for example 2 'methyl ester ( 6) Preparation:

(6) The mercaptoester (6) was prepared according to the diacid monomethyl vinegar vaporized as described in Example 1 as the ugly base. t , , , /L agent. 1H NMR (400 MHz, A-DMSO) δ 11.11 (br s, j Η) 9·00 (br s, 1 H), 8.68-8.66 : m, 2 H), 8.59 (s, 1 H), 8.44 8 41 wide

•41 (m,1 H),8·40 (d,1 H), 8.24 (s, 1 H), 8.13 (d, 1 H), 7 〇-, ( t , ·83 (s,1 H) , 7.38-7.22 (m, 8 teams 6_02 (br d' 1 H)' 5·31_5.17 (m, 3 h), 5 〇i_4 99 (5)! H), 4.97 (s, 2 H), 4.28 (dd , l H), 3.78 (dd, 1 H), 3.59 (s, 3 H), 3.38 (7) 3 H), 2.70 (m,! H), 2 58 (s, 3 h), 2 46 (d, 3 H), 2.40 (apP ^ 2 H)&gt; 2-34 (app t&gt; 2 H), 2.20-2.12 (m, 1 H), 1.65-1.54 (m, 4 H), 1.35-1.32 (m,i H), 〇87 (d, 3 H), 0 84 (d, 3 H). LCMS: Rt = 1.47 min. Example 3, Preparation of Acid (7): 121012.doc • 112·

1342310 (7) Preparation of Step 1-2' Mercaptoate·Acetate (8):

(8)

To a solution of Boc-amine-acetate (4, 190 mg, 0.153 mmol) in DCM (10 mL) was added TFA (5 mL, 67.3 mmol). The reaction was stirred for 30 minutes and concentrated. The resulting yellow squid was dissolved in DCM (10 mL) EtOAc (EtOAc m. Add adipic acid monomethyl ester gasification (0.200 ml, 1.285 mmol) to a solution of the amine salt in hydrazine (5 ml). The solution was dissolved at room temperature 121012.doc •113- Mix 10% and pour into a saturated aqueous solution of sodium hydrogencarbonate (1 mL). EtOAc (3 EtOAc) EtOAc (EtOAc) The crude product was purified by flash chromatography (EtOAc: EtOAc:EtOAc) +1280. Step 3, Preparation of the acid (7): To a solution of the methyl ester-acetate (8,170 mg, 0.133 mmol) in MeOH (100 mL) And NaOH (100 mg, 2_5 mmol). The solution was heated to 50 ° C, stirred for 2 h and concentrated to EtOAc. EtOAc (EtOAc) CM) provides 95 mg of the title compound as a tan solid. 4 NMR (400 MHz, d6-OMSO) δ 12.05 (br s, 1 H), 11.13 (br s, 1 H), 9.44 (br d, 1 H) , 8.70-8.65 (m, 2 H), 8.59 (s, 1 H), 8.45-8.42 (m, 1 H), 8.39 (d, 1 H), 8.23 (s, 1 H), 8.13 (d, 1 H), 7.82 (s, 1 H)s 7.42-7.38 (m, 1 H), 7.32 (s, 1 H), 7.29-7.17 (m, 6 H), 6.13 (br s, 1 H), 5.33- 5.17 (m, 3 H), 5.03 (d, 1 H), 4.98 (s, 3 H), 4.32 (dd, 1 H), 3.83-3.76 (m, 1 H), 3.38 (s, 3 H), 2.74-2.68 (m, 1 H), 2.58 (s, 3 H), 2.47 (d, 3 H), 2.40 (t, 2 H), 2.23 (t, 2 H), 2.19-2.14 (m, 1 H ), 1.66-1.52 (m, 4 H), 1.34-1.29 (m, 1 H), 0.87 (d, 3 H), 0.74 (d, 3 H). LCMS: Rt = 1,24 min, [M+H] + 1224. Example 4, Preparation of trifluoroacetate (9): 1210I2.doc -114·

1342310 Step 1-2, Preparation of Acetate (ίο):

To a solution of Boc-amine-acetate (4,400 mg, 0.323 mmol) in DCM (25 mL) was added TFA (5 mL, 67·3 mmol). The reaction was dropped for 30 minutes and concentrated. The resulting yellow bubble was dissolved in DCM (10 mL) and concentrated (3 repetitions). The crude amine salt was used directly without further purification. LCMS: Rt = 1.45 min, [Μ+Η] + 1138·0. To a solution of the amine (0.323 mmol) dissolved in pyridine (5 mL) was added EtOAc (EtOAc: EtOAc) The solution was stirred for 3 minutes and poured into a saturated aqueous solution of sodium hydrogencarbonate (100 ml). The mixture was extracted with Et.sub.Ac (3x) and the combined organic extracts were dried with MgSO.sub.4. On the Si02. The crude product was purified by flash chromatography ( gradient elution: 5 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ LCMS: rt = 1.67 min. Step 3, Preparation of trifluoroacetate (9): To a solution of the acetate (10' 200 mg, 〇_162 mmol) dissolved in MeOH (50 mL) _Add KAO3 (50 mg, 〇 · 362 millimoles). The reaction was stirred for 10 minutes and concentrated. The solid was suspended in EtOAc and poured into a saturated aqueous sodium hydrogen sulfate (100 mL). The mixture was extracted with EtOAc (3×) and dried with EtOAc EtOAc. The crude product was purified by HPLC (Method 1), whereby 55 mg of ethyl acetate (9) was obtained. 4 NMR (400 MHz, A-DMSO) δ 12.78 (br s, 1 Η), 9.00 (br d, 1 H), 8.69-8.67 (m, 2 H), 8.59 (s, 1 H), 8.43-8.41 (m, 2 H), 8.27 (s, 1 H), 8.19 (d, 1 H), 8.02 (s, 1 H), 7.39-7.21 (m, 7 H), 5.32-5.17 (m, 3 H) , 5.00 (d, 1 H), 4.97 (s, 2 H), 4.28 (dd, 1 H), 3.79 (dd, 1 H), 3.38 (s. 3 H), 2.70 (m, 1 H), 2.71 (m, 1 H), 2.58 (s, 3 H), 2.47 (d, 3 H), 2.20-2.12 (m, 1 H), 1.34-1.27 (m, 1 H), 0.87 (d, 3 • H ), 0.84 (d, 3 H). LCMS: Rt = 1.56 min, [M+H] + l 192. Example 5, Preparation of sulfonamide (11):

121012.doc -116- 342310 Step 1-2 Preparation of the acetate (12): rTf.

(12) To a solution of Boc-amine-acetate (4,100 mg, o.oh.m.) in DCM (25 mL) was added TFA (5 mL, 67.3 mmol). The reaction was stirred for 30 minutes and concentrated. The resulting yellow bubble was dissolved in DCM (10 mL) and concentrated (3 times). The crude amine salt was dissolved in EtOAc and EtOAc (EtOAc)EtOAc. The crude amine, which is mainly free, was used directly without further purification. LCMS: Rt = 1.45 min, [M+H] + 1138. To a solution of this amine (0,081 mmol) in pyridine (5 mL) was added methane sulfonium (0.050 mL, 0.646 m.). The solution was dispensed for 3 min and poured into a saturated aqueous solution of sodium bicarbonate (1 mL). The mixture was extracted with Et 〇Ac (3x) and the combined organic extracts were dried with &lt;RTI ID=0.0&gt;&gt; The crude acetate (12) was used in the next step without any further purification. LCMS: Rt = 1,42 min, [M+H] + 1216. Step 3: Preparation of sulfonamide (Π): 121012.doc • 117· 1342310 Add K2c〇3 (50 mg '0.362 mmol) to a solution of sulfonamide (12) in MeOH (10 ml) . The reaction was stirred for 5 min, concentrated and purified by HPLC (Method 2) to give 15 mg of sulfonamide 11.4 NMR (400 MHz, A-DMSO) δ 10.62 (br s, 1 H), 9.00 (br d, 1 Η), 8.68-B.66 (m, 2 H), 8.58 (s, 1 H), 8.44-8.41 (m, 1 H), 8.37 (d, 1 H), 8.23 (s, 1 H), 8.15 (d, 1 H), 7.39-7.20 (m, 7 H), 7.07 (br s, 1 H), 6.02 (d, 1 H), 5.31-5.18 (m, 3 H), 5.01 -4.98 (m, 1 H), 4.97 (s, 2 H), 4.27 (dd, 1 H), 3.77 (dd, 1 H), 3.38 (s, 3 H), 3.12 (s, 3 H), 2.73 -2.67 (m, 1 H), 2.58 (s, 3 H), 2.47 (d, 3 H), 2.19-2.13 (m, 1 H), 1.36-1.28 (m, 1 H), 0.87 (d, 3) H), 0.84 (d, 3 H). LCMS: Rt = 1.31 min. [M+H] + l 174. Example 6, Preparation of Amine (13):

(13) Step 1-2, Preparation of Boc-Amine (14): 12I012.doc •118· 1342310

The preparation of Boc-amine (14) was carried out according to the method described in Example 3, except that helium gas of 5-(indolyl-butoxycarbonylamino)-pentanoic acid was used as the thiolation reagent. LCMS: Rt = 1 - 66 min, [M+2H] +1 338 &lt;&quot;&quot;&gt;&gt;&gt;&gt; Add TFA (2 ml, 26.9 mmol). The solution was stirred for 30 minutes and concentrated directly onto SiO 2 . Flash chromatography (gradient elution: 0_10〇/〇

MeOH/DCM, then 100% DCM ' then 0-10% MeOH/DCM and 0.1% AcOH) afforded 90 mg of amine l3.1HNMR (400 MHz, ί/6 DMSO) 5 11.16 (br s, 1 Η), 9.23 (br d, 1 Η), 8.77 (br d, 1 H), 8.62 (br d, 1 H), 8.58 (s, 1 H), 8.44-8.42 (m, 1 H), 8.40 (d, 1 H ), 8.25 (s, 1 H), 8.14 (d, 1 H), 7.84 (s, 1 H), 7.73-7.64 (m, 2 H), 7.41 (s, 1 H), 7.35-7.31 (m, 5 H), 7.28-6.95 (m, 2 H), 6.14 (d, 1 H), 5.46 (t, 1 H), 5.29-5.25 (m, 1 H), 5.19 (dd, 1 H), 4.97 ( s, 2 H), 4.26 (dd, 1 H), 3.72 (dd, 1 H), 3.38 (s, 3 H), 2.85-2.79 (m, 2 H), 2.71-2.65 (m, 2 H), 2.59 (s, 1 H), 2.46 (d, 3 H), 2.44-2.42 (m, 2 H), 2.22-2.15 (m, 1 •119· 12I0I2.doc Η), 1.96 (s, 3 Η), 1.70-1.56 (m, 4 Η), 1.50-1.42 (m, 1 Η), 0.88 (d, 3 Η), 0.84 (d, 3 Η). LCMS: Rt = 1.06 min, [M+2H] + 1238. Example 7, Preparation of Amine (15):

Boc-amine (15) was prepared as described in Example 6. The acetate protecting group was then removed according to the procedure described in Example 4. The boc protecting group was removed according to the procedure described in Example 6. Purification by HPLC (Method 1) provides the amine (15). Towel NMR (400 MHz, A-DMSO) δ 11.16 (s, 1 Η), 9.02, (br d, 1 Η), 8.70-8.65 (m, 2 Η), 8.60 (s, 1 Η), 8.45-8.41 (m, 1 Η), 8.40 (d, 1 Η), 8.24 (s, 1 Η), 8.13 (d, 1 Η), 7.84 (s, 1 Η), 7.69-7.62 (br s, 3 H), 7.38-7.20 (m, 7 H), 6.03 (br s, 1 H), 5.31-5.18 (m, 3 H), 5.02-4.99 (m, 1 H), 4.97 (s, 2 H), 4.28 (dd , 1 H), 3.78 (dd, 1 H), 3.38 (s, 3 H), 3.12-3.06 (m, 4 H), 2.84-2.79 (m, 2 H), 2.73-2.69 (m, 1 H) , 2.58 (s, 3 H), 2.47 (d, 3 H), 2.46-2.42 (d, 3 H), 2.20-2.12 (m, 1 H), 1.70-1.54 (m, 4 H), 1.29-1.22 (m, 1 H), 1.17 (t, 6 H), 0.87 (d, 3 H), 0.84 (d, 3 H). LCMS: Rt = 0.93 min, [M+2H] +1196. 121012.doc -120- 1342310

Indoleamine (16) was prepared according to the procedure shown in Example 3. 1H NMR (400

MHz, c?6-DMSO) δ 10.69 (s, 1 Η), 9.00 (br d, 1 H), 8.68-8.66 (m, 2 H), 8.59 (s, 1 H), 8.45-8.41 (m, 1 H), 8.40 (d, 1 H), 8.25 (s, 1 H), 8.16 (d, 1 H), 7.87 (s, 1 H), 7.39-7.21 (m, 7 H), 6.03 (br s , 1 H), 5.31-5.18 (m, 3 H), 5.01-4.99 (m, 1 H), 4.97 (s, 2 H), 4.27 (dd, 1 H), 4.18 (s, 2 H), 3.78 (dd, 1 H), 3.70-3.68 (m, 2 H), 3.63-3.59 (m, 4 H), 3.52-3.50 (m, 2 H), 3.38 (s, 3 H), 3.24 (s, 3 H), 2.73-2.68 (m, 1 H), 2.58 (s, 3 H), 2.47 (d, 3 H), 2.20-2.12 (m, 1 H), 1.35-1.28 (m, 1 H), 0.87 (d, 3 H), 0.84 (d, 3 H). LCMS: Rt = 1.45 min, [M+H] + 1256. Example 9, Preparation of Acid (17) 121012.doc -121 - 1342310

(17) Step 1: Preparation of guanamine (18)

Add CS2CO3 (100 mg '0,309 mmol) and methyl iodide (0.100 mL) to a solution of Boc-amine-acetate (3,200 mg, 167 mM) in DMF (5 mL). 1.61 millimolar, neutralized with Al2〇3). The solution was stirred for 2 hours, concentrated and used in the next step without further purification. LCMS: Rt = 1.85, [Μ+ϋ;1 + 12ΐ{) 〇Step 2-4: Acid (17) Preparation of acid ( 17) According to Example 3, MHz, ί/5-DMSO) δ 9.01 8-59 (s, 1 Η), 8.45-8.41 beer. Η NMR (400

(br d, 1 Hs R (m, 1 HU.w (I9·8.66 (five) 2 H), (d, 1 H), 8.26 (s, 1 121012.doc, 122· P42310 Η), 8.22 (d, 1 Η), 7.92 (br s, 1 H), 7.39-7.20 (m, 8 H), 5.31-5.18 (m, 3 H), 5.00-4.99 (m, 1 H), 4.97 (s, 2 H), 4.27 (dd, 1 H), 3.81-3.76 (dd, 1 H), 3.38 (s, 3 H), 3.34 (br s, 3 H), 2.73-2.68 (m, 1 H), 2.58 (s, 3 H), 2.47 (d, 3 H), 2.46-2.40 (m, 2 H), 2.26-2.41 (m, 2 H), 2.19-2.12 (m, 1 H), 1.80-1.73 (m, 2 H) , 1.33- 1.25 (m, 1 H), 0.88 (d, 3 H), 0.84 (d, 3 H). LCMS: Rt = 1·27, [M+H] +1224. Example 10, acid (19) Preparation

Acid (19) was prepared according to the procedure described in Example 3. fH NMR (DMSO-^) δ 11.22 (s, 1 Η), 9.27 (d, 1 Η), 8.65-8.69 (m, 2 Η), 8.58 (s, 1 Η), 8.42-8.45 (m, 1 Η) ), 8.38 (d, 1 Η), 8.23 (s, 1 Η), 8.13 (d, 1 Η), 7.83 (s, 1 Η), 7.19-7.46 (m, 8 Η), 6.42 (br s, 1 Η), 5.18-5.30 (m, 3 Η), 5.02 (d, 1 Η), 4.98 (s, 2 Η), 4.27-4.34 (m, 1 Η), 3.77-3.82 (m, 1 Η), 3.38 (s, 3 Η), 2.69-2.74 (m, 2 Η), 2.58 (s, 3 Η), 2.41-2.46 (m, 5 Η), 2.14-2.23 (m, 3 Η), 1.79-1.85 (m , 2 Η), 1.28-1.34 (m, 1 Η), 0.83-0.88 (m, 6 H). LCMS: Rt = 1.18, [M+H] +1 210. 121012.doc -123 - 1342310 Example 11, Preparation of Acid (20)

Acid (20) was prepared according to the procedure described in Example 3. iH NMR (DMSO-^5) δ 11.18 (s, 1 Η), 9.00 (d, 1 Η), 8.67 (d, 2 Η), 8.59 (s, 1 Η), 8.42 (d, 2 Η), 8.24 (s, 1 Η), 8.14 (d, 1 Η), 7.80 (s, 1 Η), 7.22-7.38 (m, 8 Η), 5.18-5.31 (m, 3 Η), 5.00 (d, 1 Η) , 4.97 (s, 2 Η), 4.24-4.30 (m, 1 Η), 3.75-3.81 (m, 1 Η), 3.38 (s, 3 Η), 2.63-2.73 (m, 2 Η), 2.58 (s , 3 Η), 2.53- 2.56 (m, 1 Η), 2.46-2.48 (m, 5 Η), 2.13-2.19 (m, 1 Η), 1.29-

1.35 (m, 1 H), 0.83-0.88 (m, 6 H). LCMS: Rt = 1.22 min, [M+H] + l 196. Example 12, Preparation of Amine (21)

121012.doc -124- 1342310 The amine (2丨) was prepared according to the procedure in Example 7.咕nmr (DMs〇^^ δ 9.01 (d,l Η), 8.65-8.69 (ίη,2Η)&gt;8 59 (δ5ΐΗ)58 39_8 44 (m,2H), 8.24(s'lH), 8.13(d , iH), 7.83 (s, lH), 7.20- 7.37 (m, 8 Η), 6.02 (d, 1 η), 5.18-5.31 (m, 3 Η), 5.00 (d, 1 Η), 4.97 (s , 2 Η), 4.24-4.30 (m5 λ 3.76-3.81 (m, 1 Η), 3.38 (s, 3 Η), 2.66-2.72 (m, 3 Η), 2.58 (s, 3 Η), 2.44-2.4 (m, 5 Η), 2.14-2.18 (m, 1 Η), 1.72-1.79 (m, 2 Η), 1.24-1.33 (m, 1 Η), 0.83·0.88 (m, 6 Η). LCMS : &amp ; = 〇%, [Μ+Η]+1181. Example 13, Preparation of Amino Thiazole Hydrogen Acid (22)

Hydrogen acid was bubbled through a solution of Boc-protected amine (4,1 - 4 g, 1.1 mmol) in DCM (20 mL) for 30 min. The reaction mixture was then sealed and stirred for 30 minutes, after which time the reaction mixture was bubbled with nitrogen. The mixture loses its gelatinous appearance. DCM (5 ml) was added to the solution and the HC1 gas was bubbled through it for another 20 minutes, then nitrogen was bubbled for 3 Torr. After concentrating, the title compound was obtained mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjJ Example 14, Preparation of Acid (23):

• (23) Step 1, using iV-cyclohexylcarbodiimide, methyl polystyrene coupling reaction to aminothiazole hydrogen acid (22,348 mg, 1 equivalent) dissolved in DCM (20 mL) and pyridine ( Add 1 (-)-4-mercaptosuccinic acid 1-monomethyl ester (72.0 μl '0.45 mmol, 2 equivalents) and cyclohexylcarbodiimide, TV'- Mercapto polystyrene (348 mg, 0.90 mmol, 3 equivalents). The reaction mixture was stirred for 4 hours, then the solution was filtered through celite and concentrated. Step 2' deprotection of the acetate and saponification to the acid

The concentrate was dissolved in THF (5.0 mL), MeOH (EtOAc) To this solution was added 4 M LiOH (0.34 mL, 3.96 mmol). An ammonium sulfate (saturated aqueous solution) was added to neutralize excess Li 〇 H, and the solution was concentrated to cerium oxide. The first time the crude residue (isocratic) was chromatographed with i〇0/〇 Me〇H in the middle. A second chromatography (gradient elution: 〇-10% MeOH / DCM) gave product. HRMS [m+h]+ 1224 2688. 121012.doc -126· 1342310 LC Rt = 14.85 minutes. Example 15, Preparation of Amino-Acid (24):

• (24) Step 1: The conditions for the coupling of the 24 amide are the same as in Example 14, except that Step 1 uses Boc-(L) decyl phthalate (27.3 mg, 〇.〇9 mmol) . Step 2: The procedure in Example 5 was used to remove the acetate protecting group. Flash chromatography (50-80% ethyl acetate / hexanes) afforded 239 mg. Step 3: Deprotection of Boc and the third-butyl group

The material was dissolved in DCM (50 mL) and HCl was then bubbled from the solution for 10 min and then the solution was bubbled with nitrogen to remove excess acid. Purification by HPLC gave 24 (9 mg). LCMS: Rt = 〇 99 min, [M+2H] + 1226 Example 16. Preparation of sulfonamide (25): 12l012.doc -127- 1342310

(25) Step 1: • Add 2-phenyl phthalimide to a solution of aminothiazole hydroformate (22, 1 g, 〇85 mmol) in pyridine (30 mL) The brewing gas (700 mg, 2.6 millimoles). The reaction was stirred for 2 hours. After additional sulfonium (236 mg, 1.3 mmol) was stirred for 30 minutes, the mixture was concentrated to silica gel and purified by flash chromatography (gradient elution: 5 〇 〇〇 EtOAc / hexane) The product was obtained (5 〇 0 mg). Step 2: Deprotection of o-bromoimine. To a solution of sulfonamide dissolved in MeOH (30 ml) was added hydration tillage # (0.5 ml). The mixture was stirred for 1 hour and the mixture was concentrated onto a pad of silica eluting with flash chromatography (gradient elution: 0-10% MeOH / DCM then 1% NH4OH + 10% MeOH / DCM). Purification was carried out using a Biotage column C18 (gradient elution: i _ _ 70 〇 / 0 c s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s Example 17, Preparation of Phosphoric Acid (26) 121012.doc -128- 1342310

Step 1: The tanning amine synthesis of compound 26 was carried out using diethyl phosphate valeric acid (0.2 mL) and PS-DCC according to the procedure described above. Step 2: Deprotection of Phosphoric Acid TMSBr (1 mL, &gt; 100 equivalents) was added to a cooled solution of phosphoester (275 mg, 0.21 mmol) dissolved in DCM (50 mL). The mixture was stirred for 1 hour and then allowed to warm to room temperature. TMSBr (2 ml, &gt; 100 equivalents) was added and the solution was stirred at room temperature for 1 hour. The mixture was concentrated to dryness and the crude phosphoric acid was used directly without further purification. Step 3: Acetate removal was carried out according to the procedure described above. Purification was carried out on a C18 biotage column. Two purifications (gradient elution: 20-80% acetonitrile/water and 0.1% TFA; second column 20-80% acetonitrile/water and 0.1%) were carried out to obtain product 26. HRMS: m/2 = 630.6124, LC Rt = 13.24 min. Example 18, Preparation of alcohol (27): 1210l2.doc -129- 1342310

(27) Add acid 23 (1.0 g, 0.82 mmol) to THF (2 mL) in THF (2 mL) Domain (0_08 ml, 〇.89 mmol). The mixture was stirred for 3 minutes and then allowed to warm to room temperature and stirred for additional 30 minutes. The triethylamine hydrogenate was filtered off and the solution was again cooled to 〇 °C. NaBH4 (68 mg, 1.8 mmol) in water (3 mL) was added. The mixture was stirred for 3 minutes, warmed to room temperature and stirred for a further 30 minutes. The mixture was neutralized with 1 n HC1 and partitioned with DCM. Organic extracts were collected and concentrated. By chromatography: column i, 81 (^ Lu 6 (: 18 column, gradient elution 20-70. / acetonitrile / water and 0.1% butyl into the pure _ product. The second purification of the column 1 The third purification was performed using a Biotage C18 column (gradient elution: 20-70% acetonitrile/water and 0.1% ammonium sulphate) to afford product e LCMS Rt = 1.37 min, [M+H] +1 210. 19, Preparation of acid (28): -130· I21012.doc 1342310

(28) Step 1:

The indoleamine synthesis of compound 28 was carried out using the trans-4-carbonylmethoxycyclohexane-l-carboxylic acid (316 mg, 1.70 mmol) according to the PS-DCC procedure described above. Step 2: Deprotection and saponification of the acetate used in Synthesis 28 was carried out according to the procedure described above. Purification by flash chromatography (isocratic elution: 10% MeOH / DCM) LCMS: Rt = 1.37 min, [M+H] + = 1250. • Example 20, Preparation of Amino-decylamine (29):

(29) 12I012.doc -131 - 1342310 to 28 (470 mg, 0.38 mmol) dissolved in acetone (2 mL), water (3 μL) and EhN (0, 2 mL, 1.5 mmol) Ethyl formate (0.07 mL, 0.75 mmol) was added to the solution. The solution was stirred for 1 hour and ethylamine (0.53⁄4 liters, 7.5 mmol) was added and the crude solution was concentrated to EtOAc and flash chromatography (gradient elution: 0-20% MeOH/DCM) Purification was carried out via HPLC to give the product as a yellow solid. [[jjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj

(30) Step 1: Add alcohol (0.354 g, 3. 〇〇 mmol) to the suspension of hydrazine nitrogen 2 (1.15 g, 1.00 mmol) in toluene (6 mM) and in the rib It stirred the mixture for 4 hours. The reaction was concentrated in EtOAc (yield: EtOAc (EtOAc)). Step 2: Add sodium hydroxide (0 325 g, 8.13 mmol) to a solution of the ester (1.01 g, 0.815 mmol) dissolved in EtOAc (25 mL) and water (3 mL) The mixture was stirred at 121012.doc • 132· 1342310 22 ° C for 16 hours. The reaction was quenched by gamma and the crude product was purified by flash chromatography (MeOH / DCM) to yield &lt;RTIgt; LC: Rt = 14.83 min, HRMS: [M+H] + 1226.2257. Example 22, Preparation of Amidino-Acid (31):

(31) Step 1: Add trans-4-hydroxy-cyclohexanecapric acid ethyl ester to a suspension of hydrazine (2' 0.600 g, 0.522 mmol) in toluene (20 mL) (0.134) g '0.778 mmol> and the mixture was stirred at 80 ° C for 5 hours. The reaction was thawed in vacuo and the crude material was purified by flash chromatography (MeOH / DCM) to yield &lt;RTIgt; Step 2: To a solution of the vinegar (0.236 g, 0.182 mmol) dissolved in THF (3.6 mL) and H.sub.2 (1.2 mL) was added lithium hydroxide (45 g, j 29 mmol) and The mixture was stirred at 22 ° C for 48 hours. The reaction was concentrated in EtOAc (yield: EtOAc/EtOAc). Further purification was obtained by hplc (30 X 100 mm 121012.doc -133-1342310 C18 Waters Sunfire 'gradient elution 30-80% ACN/H2 〇, 〇.ι〇/. TFA, 6 ml/min for 9 minutes) . LC: Rt = 12.98 min. HRMS: m/2, [M+2H]+ 633.6321. Example 23, Preparation of urea (32):

(32) Step 1 : To a solution of the amine 22 (0.115 g, 0-101 mmol) in pyridine (4 ml), ethyl 3-isocyanotopropanoate (0.452 ml, 0.343 mmol) The mixture was stirred at 22 ° C for 1 hour. The reaction was concentrated in EtOAc and the residue was taken from toluene to afford 0.129 g (0.101 mmol) of EtOAc. LCMS: m / 2 [M+2H] + 641. Step 2: To a solution of the acetate (0.129 g, 0.11 mmol) in MeOH (4 mL) was added K2C03 (42 mg, 0.303 mmol) and at 22. (The mixture was stirred for 2 hours. NaOH (solid, 100 mg, 2.5 mmol) dissolved in H20 (2 mL) was added via syringe and the reaction mixture was stirred for 24 hours. Volatile component. Purify the residue by 1^1^(:(30-80% ACN/H20, 0.1% TFA) to give 30 mg 121012.doc • 134- () color solid 32. LC : Rt = 16.69 minutes, MS [M+H] + 1211 Example 24, Preparation of sulfonyl urea (3 3):

(33) Step 1: Add a third _Bu〇H (918 μl, 9沁) to a solution of the isocyanate (I", 9.6 mmol) dissolved in DCM (50 mL) at 〇C. Molly) and stir for 30 minutes while maintaining the temperature at 〇. Add 〇2 μ continuation of the brewing solution to the solution of the amine 22 (82 〇 mg '0.72 mmol) dissolved in pyridine (12 ml) (1.44 Millol '0.72 ml). The reaction was stirred for 5 minutes at 〇t. The solvent was evaporated in vacuo </ RTI> and was subjected to a flash chromatography (gradient elution: 0-10% MeOH/DCM) The solid was purified to give 220 mg of boc- sulphonylurea. MS (M+H) +1 317 &lt;&quot;&gt;&gt;&gt;&gt; Step 2: To the intermediate boc-sulfonylcarbazide (106 mg, 0.08 mmol) dissolved in MeOH (10) K2C〇3 (111 mg, 〇.8 mmol) was added to the solution in ML). The reaction was stirred at 22 ° C for 2 hours. 1 g of SiO 2 was added to the reaction and evaporated in the stencil T The solid was purified by flash chromatography (EtOAc EtOAc:EtOAc:EtOAc) Doc -135 - 1342310 liters), cooled to 〇t and bubbling HC1 (gas) into the solution for 1 Torr. The reaction was blocked and stirred for 2 hours. N2 gas was bubbled into the reaction to remove excess HC1 gas. The solvent was evaporated in vacuo to afford 14 mg of crude yellow solid. The solid was purified by HPLC (gradient elution: 30-50% ACN/H20, 0.1% TFA) to afford 11 mg of 60% purity solid. Sub-HPLC purification (gradient elution: 50-55% ACN/H20, 0.1% TFA) afforded 6.7 mg of product 33. LCMS: Rt 1.24 min '(M+H) + 1175 » Scheme 3: Synthesis of imidazole

121012.doc -136-

Example 25, Preparation of imidazole (37): t^0H Η

Step 1 : To a suspension of boc-amine 4 (800 mg, 0.647 mmol) in DCM (5 mL) was added HCl (gas, stream) for 20 min. The reaction was applied to the reaction and the mixture was disturbed for 30 minutes. The reaction was concentrated to dryness and used in the next step without further purification. The residue was suspended in DCM (150 mL) and a solution of formic acid in &lt;RTI ID=0.0&gt;&gt; The crude amylamine (34) was concentrated to dryness and stored at 4 hours for 4 hours. LCMS: Rt 1.46 min, [M+H] + 1166. Step 2: Add DIPEA (1 ml ' 5.74 mmol) and hydrazine (: 13 (1 〇〇 microliter) to the suspension of the intermediate medramine (34 '670 mg) in DCM (100 mL) ' 1.27 millimolar The reaction was stirred for 3 minutes at room temperature and a second portion of DIPEA (1 mL, 5.74 mmol) and p〇Cl3 (1 μL, 1.27 mmol) was added. The reaction was stirred for a further 3 hrs and then concentrated to EtOAc (EtOAc: EtOAc (EtOAc:EtOAc) 35) LCMS: Rt 1.72 min, [Μ] 1148. Step 3: Add Cu20 (catalyst) to a solution of isonitrile (35, 100 mg, 0.087 mmol) dissolved in THF (8 mL) Ethyl cyanoacetate (13.8 mg, 0-122 mmol) and phenanthroline (3.1 mg, 0. 017 mmol). The reaction was placed in a closed tube and heated to 80 ° C for 2 hours. It was then cooled to room temperature. The reaction was concentrated and purified by flash chromatography (gradient elution: 50-100% EtOAc in heptane); second column: (gradient elution · · 〇·ι Purification with % MeOH in DCM to provide the imidazole-ester 36. LCMS: Rt 1.62 min, [M+2H] + 1262. Step 4: Toluene 36 in MeOH (8 mL) and H20 (2 mL) NaOH (solid, 10 mg, 0.25 mmol) was added to the solution and the reaction was heated to 40 ° C for 12 h. The reaction was cooled to room temperature and concentrated to dryness. Deprotection: 45-55% acetonitrile in H20 and 0.1% TFA). The final purification yielded 3 mg of TFA salt. LCMS: Rt 1.13 min, [M+H] + 1 191. Example 26, imidazole (38) Preparation:

(38) 121012.doc -138- 1342310 Step 1: Add PS- to the suspension of crude imidazole 37 (180 mg '0.151 mmol) in DCM (10 mL) and pyridine (500 μl) DCC (0.453 mmol) and amino-acetic acid methyl ester (20 mg, 0.227 mmol). The reaction was stirred at room temperature for 48 hours and then heated to 40 °C for 2 hours. The residue was concentrated onto EtOAc and purified by flash chromatography ( gradient eluting: 50-1 EtOAc EtOAc LCMS: Rt 1.35 min, [M+H] + 1262. Step 2: The methyl ester (77 mg, 0_061 mmol) was suspended in MeOH (5 mL) and H20 (1 mL) and NaOH (solid, 40 mg, 1.00 mM). The reaction was stirred at room temperature for 12 h and then concentrated to EtOAc (EtOAc:EtOAc:EtOAc:EtOAc : Rt 1.18 min, [M+2H] + 1249 〇 Example 26, Preparation of imidazole (39):

Step 1: 121012.doc -139· 1342310 To a crude succinic acid 37 (276 mg, 0.232 mmol) in DCM (20 mL). PS-DCC (0.695 mmol) and (R)-nt-rrolidine-2-carboxylic acid methyl ester (60 mg, 463·463 mmol) were added to the suspension in the bite (1.0 ml). The reaction was stirred and heated to 40 °C for 24 hours. The reaction was concentrated to EtOAc (EtOAc) elute elute elute LCMS: Rt 1.45 min, [m+2H] + 1303. Step 2: The methyl ester (170 mg, 1.305 mmol) was suspended in MeOH (10 mL) and H20 (2 mL) and NaOH (solid, 40 mg, 1.00 mM). The reaction was stirred at room temperature for 18 hours and then heated to 40 °C for 12 hours. The reaction was loaded onto silica gel by flash chromatography (gradient elution: (MO% MeOH in DCM)) followed by HPLC (gradient elution: 40-60% acetonitrile in H20 and 0.1% TFA). 5 mg of succinic acid 39. LCMS: Rt 1.11 min, [M+H] + 1288. Biological results: using the standard MIC test described above and Enterococcus faecalis, Enterococcus faecium or Staphylococcus aureus, compounds 5-7, 9, 11, 13, 15-17, 19-21, 23-25, 27-33, 37-39 exhibit between 0.00 10 μg/ml and 128 μg/ml The minimum inhibitory concentration between the two. Equivalents Those skilled in the art will be able to understand or determine many equivalents of the specific embodiments and methods described herein using only routine experimentation. The equivalents are all: 140- 12l012 .doc 1342310

It is intended to be included within the scope of the following claims. Incorporation by Reference Therefore, the entire contents of all patents, published patent applications, and other references cited herein are hereby expressly incorporated by reference in their entirety in their entirety in

Claims (1)

1342310 Patent Application No. 096119338 Chinese Patent Application Substitution (November, 1999) X. Patent Application Range: 1. A compound of formula VII: R VII and a pharmaceutically acceptable salt thereof; wherein R is selected from the group consisting of Ν(Ι^)2 and l^Rb-AGQJ; A is a linkage or is selected from the group consisting of: -&lt;:(0 )-, -(:(0)(:(0)-, -C(0)0-, -C(0)N(R8a)-, -S(0)2-, -S(0)-, , -S(0)2N(R8a)_, -S(0)N(R8a)-, -C(=NR8)N(R8a)-, -C(=NR8)N(R8a)C(0)- , -C(=NR8)-, -C=CC(0)-, -C=CC(0)0-, -C=CC(0)N(R8a)-; G does not exist, is selected from the following consisting of Group: -[C(Ra)(Rb)]x-' -[C(Ra)(Rb)]xC(Ra)=C(Ra)-[C(Ra)(Rb)]y- &gt; -[ C(Ra)(Rb)]x-121012-991110.doc H42310 〇-[C(Ra)(Rb)]y• and -, or selected from -(cycloalkyl)-, -(heterocyclic)_, · (aryl)_ and _(heteroaryl)_ group of groups 'each of which has 0-4 substituents' wherein the cycloalkyl group contains 3 to 10 carbon atoms; Q is absent, selected from -C (0)-[C(Ra)(Rb)]x-, -C(0)-[C(Ra)(Rb)]xC(R&gt;C(Ra)-[C(Ra)(Rb)]y - ^ -C(0)-[C(Ra)(Rb)]x-〇-[C(Ra)(Rb)]y- and -(:(〇ΗΝ(Μ3Η(:(ι^)(ν) Κ}ρ-group of groups, or selected from the group consisting of: -(cycloalkyl)_, _(heterocyclic)_, _(aryl)_, _(heteroaryl)- , -c(o)-(cycloalkyl)·, _c(〇h heterocycle)-, -c(o)-(aryl)· and -C(0)-(heteroaryl)-, each of which One has 〇4 substituents, wherein the cycloalkyl group contains 3 to 10 carbon atoms; J is selected from the group consisting of Η, Cl 4 alkyl, halogen, Cl. 4 alkoxy, thiol , Amino, mono- and di-Cl 4 alkylamino, triCl 4 alkyl, alkyl, c〇2H, C(=〇)N(R8a)2, CH2C02H, CH2C(=0)N(R8a 2, CCVCm alkyl, C(0)CBu 4 alkyl, P(0)(0H)2, PiOMO-Cw alkyl)2, c0.4 alkyl-(cycloalkyl) and CG_4 a base-(heterocyclic ring) which may be substituted 0-4 times, wherein the cycloalkyl group contains 3 to 10 carbon atoms; the Ra system is selected from the group consisting of hydrazine, alkyl, F, CO 2 H, C02- An alkyl group, -N(R 丨) 2 ', 〇R 丨, _(ch2)0.4-J and -R4b, wherein the alkyl group contains 1 to 10 carbon atoms; and Rb is selected from the group consisting of ruthenium, alkyl and F. a group wherein the alkyl group contains from 1 to 10 carbon atoms; ρ is 0, 1, 2 or 3; 121012-991110.doc 1342310 y and y are each independently selected from an integer between 〇1〇 ; R mother occurrence is independently selected from And a substituted C group and rC, wherein the alkyl group contains 1 to 10 carbon atoms; the ruler is selected from the group consisting of alkyl and _(CH2_CH2_〇_)n_R9 wherein η is the following integer: moo, ! , 〇〇〇, 2 〇〇〇, 3 〇〇〇, 4 〇〇 (), 5.000, 10, _, 20, _, 30, _, 40, _, 5 〇, _ or 60,000 or the following values The average of the integers: 1, 〇〇〇, 2,000, 3,000, 4 000, 5 〇〇〇, 1 〇〇〇〇, 30.000, 40, _, 5 〇, _ or 6 〇, _, which burns The base contains ^ carbon atoms; ll-6 yard burst R is selected from the group consisting of H ' CN, Ν〇C3-7 cycloalkyl and S〇2-CN6 alkyl; and R does not exist, or choose Free of the following composition group C丨-6 alkyl, c3-7 cycloalkyl, J substituted C| 6 fen and R4b, or two R8a residues = merging can form 3 to 7 rings A saturated, unsaturated or aromatic ring of an atom which can be substituted 4 times. 2. The compound of claim 1, Α-G-Q-J, to form η, or a flyer to form a functional group selected from M consisting of: -tR#N(R»).A.G-Q.j, R»#h 121012-991110.doc 1342310 121012-991110.doc -4- 1342310 121012-991110.doc 1342310 3. The compound of claim 1, wherein R is MR^AGQJ, R1 is Η and AGQJ together forms a functional group selected from the group consisting of: ^^r13 〇, r13 〜K, r13 /, r13 /,!K, r13 Wherein R13 is selected from the group consisting of hydrogen, hydroxyindenyl and aminoguanidino groups or selected from the group consisting of: 121012-991110.doc -6- 1342310 121012-991110.doc 1342310 Η-system 歹, integer of J: 1-500, 1,000, 2,000, 3,000, 4,000, 5.000, 10,000, 20,000, 30,000 '40,000, 50,000 or 60,000 or an average of the integers of the following values: 1-500, 1.000 , 2,000, 3,000, 4,000, 5,000, 10,000 '20,000 ' 30.000, 40,000, 50,000 or 60,000 ° 4. The compound of claim 1, wherein A is C(O), C(0)0 or C(0)NH; G is a C 4-7 bad burn group, Q is absent; and J is CO 2 H or COA w alkyl. 5. A compound selected from the group consisting of: 121012-991110.doc 1342310 /=Γί 121012-991110.doc 1342310 121012-991110.doc -10- 1342310 1210l2-991110.doc 1342310 121012-991110.doc -12- 1342310 121012-991110.doc -13- 1342310 ο P-OH II 121012-991110.doc 14 1342310 121012-9911I0.doc 15 1342310 OH 121012-991U0.doc • 16- 1342310 121012-991110.doc 17 —1342310 0\ OH f=( 121012-991110.doc -18- 1342310 And 6. Use of a compound according to claim 1 for the manufacture of a medicament for the treatment of bacterial infections. 7. Use of a compound according to claim 1 for the manufacture of a medicament, 121012-991110.doc -19-B42310 for the manufacture or prevention of EF-Tu activity. 8. Use of a compound according to claim 1 for the manufacture of a medicament for the treatment of a sore. 9. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable carrier or diluent. 121012-991110.doc -20-